This is the third post telling the story of how I discovered that adverse events are risk factors for type 1 diabetes (post 1), asthma (post 2) and other chronic illnesses. I never learned this as a physician.
The risk factors I found for type 1 diabetes and for asthma came from solid, well-respected science that remains virtually unrecognized in medical care and outside of research studies today.
Table of Contents
- 1 Introduction
- 2 Maternal Behaviors Affect Genes
- 3 Chronic Disease, Epigenetics and Stress
- 4 Mother-Baby Contact Affects Epigenetics in Children
- 5 The Effects of Experience Can Last a Lifetime
- 6 Maternal Experiences Affect Generations
- 7 Genes Are Affected During Sensitive Periods
- 8 The Sensitive Period After Birth
- 9 Supporting Moms: Supporting Generations
- 10 Treatment and Research
- 11 What You Can Do
- 12 What About You? Does This Make Sense of Your Illness?
- 13 Let Me Know In a Comment
The first post in the causes of chronic illness series describes Swedish researcher Gisela Dahlquist’s finding that risk for type 1 diabetes increases when babies are separated from their mothers after birth.
The second post shows you how psychologist Tony Madrid accidentally discovered that maternal-infant separation interferes with bonding and is one of the important risk factors for asthma. His studies further identified that risk
- for separation was triggered by difficult experiences such as pregnancy and birth complications,
- was the same whether separation was physical or emotional,
- resulted from events that were outside of a mother’s control,
- occurred because it interrupted mothers’ capacities to bond with and nurture their babies.
Tony treated these mothers for the sense of loss, grief or other often painful feelings that were frequent results of physical and emotional separation from their babies in early life. Most of their asthmatic kids healed completely with this intervention (1)Madrid, A. (2010). The Mother and Child Reunion: Repairing the broken bond. Monte Rio, Lulu Press.
I long wondered how treating an asthmatic kid’s mother could lead to recovery from a chronic illness in her child. That’s what today’s post addresses.
A 2004 ground-breaking study offered an explanation.
We may have genes that increase our risk of developing a particular disease such as type 1 diabetes or asthma. But having such a gene does not mean we will develop the illness.
Whether our gene is expressed and a disease develops ALSO requires interaction with our environments.
Research shows that adverse life experiences are important environmental risk factors that influence risk for chronic illness.
Life experiences influence our genes via epigenetics
Michael Meaney is a behavioural epigeneticist and neurobiologist at McGill University in Montreal, Quebec. He and his colleague Moshe Szyf, a molecular biologist and geneticist, published a landmark study in 2004 showing that maternal behaviors in rats influence genetic expression in their pups (2)Weaver, I. C., et al. (2004). “Epigenetic programming by maternal behavior.” Nat Neurosci 7(8): 847-854. This happens through epigenetics.
Genes are turned on and off by the presence of small chemicals that bind to them.
Epigenetics refers to the study of how these little molecules affect gene expression without changing the underlying structure of our DNA.
The small molecules that attach to genes are affected by life experiences. These events influence gene expression during growth and development in pregnancy and childhood, telling which cells to grow into heart cells or brain cells, muscle cells and nerve cells, among many other functions.
These molecules also affect nervous system regulation through the HPA axis (hypothalamic-pituitary-adrenal) and other areas to regulate responses to stress.
Ultimately, epigenetics influence physiology. This includes processes such as blood pressure, breathing, temperature and more.
Epigenetics is nature’s built-in mechanism that enables each one of us to adapt and respond to our unique environments, including the environment of experience.
This is where links between chronic disease, epigenetics and stress come in.
More nurtured pups are less sensitive to stress
Meaney and Szyf’s group found that rat pups raised by nurturing dams, who use more licking, grooming and arching behaviors (arching their backs exposes their bellies and makes it easier for pups to nurse), differed from pups raised by rat mothers that licked, groomed and arched less.
The more highly nurtured pups were less reactive to stress.
They discovered that the calmer pups had epigenetic changes to genes that regulate cortisol and stress responses.
These genes had different amounts of epigenetic attachments (methyl groups) compared with pups raised by less nurturing dams.
Their study is one of the first and most cited studies showing that maternal behaviors affect genes in offspring.
These findings provided insights about the effects of risk factors in early life. They offer insights into why prenatal stress, adverse events during labor and birth, stress and trauma in infancy can influence risk for chronic health conditions later in life.
The links between chronic disease, epigenetics and stress are beginning to explain why the effects of life experiences on health are not because chronic illness is psychological, psychosomatic or all in your head.
Instead, it’s showing us that life events affect health by the way they interact with our genes.
Maternal behavior affects safety & perceptions of threat
Meaney and Szyf’s studies revealed that a mother’s behaviors influence her offpsring’s sense of safety and perceptions of threat.
Through … epigenetic processes, maternal effects influence the development of defensive responses to threat in organisms ranging from plants to mammals.
In the rat, such effects are mediated by variations in maternal behavior, which serve as the basis for the transmission of individual differences in stress responses from mother to offspring (3)Weaver, I. C., et al. (2004). “Epigenetic programming by maternal behavior.” Nat Neurosci 7(8): 847-854, p. 847.
This offered a vastly different context and interconnected perspective regarding the role of early life events as risk factors for asthma. And also for type 1 diabetes.
It wasn’t that these diseases were psychological.
It was because certain kinds of life experiences affect perceptions of threat at the cellular, nervous system and physiological levels.
Research in epigenetics provides tremendous insights into the mechanisms by which adverse life experiences affect risk for chronic illness.
Chronic Disease, Epigenetics and Stress
In Meaney’s studies, the epigenetic effects were seen whether mother rats were the biological mothers or foster mothers who shared none of the same genes with the pups.
This meant that pups were calmer not because of the genes they inherited, but because their genes had been turned on or off after a particular experience.
In this particular set of studies, genes were being altered as a result of experiences that heightened offsprings’ perceptions of threat.
What the research I discovered and have described in the first three blog posts of this discovery series suggests that a mother’s experiences affect her child’s long-term health. As well as his or her risk of – or protection from – developing a chronic illness.
The first epigenetic study looking at effects of human maternal contact on children was published in 2017.
Mother-Baby Contact Affects Epigenetics in Children
Sarah Moore is a postdoctoral student at the University of British Columbia’s Children’s Hospital Research Institute. She went there to study in Professor Michael Kobor’s lab in the Department of Medical Genetics. Moore is the first author of a study published in November 2017 that eloquently summarizes research showing how life events alter genes, especially in early life.
Her study found that the degree of mothers’ physical contact with their 5-week-old infants was linked to epigenetic changes 4 years later (4)Moore, S. R., et al. (2017). “Epigenetic correlates of neonatal contact in humans.” Dev Psychopathol 29(5): 1517-1538.
As she and her co-authors state, the science of epigenetics reflects “the biological embedding of early experiences.” This is how life events shape long-term health as well as resilience.
In the study, 94 mothers kept a diary for 4 consecutive days when their babies were 5 weeks old. This included activities such as sleeping, crying, fussing, feeding and the duration of any bodily contact. When the children were 4-and-a-half years old the inside of their cheeks were swabbed for DNA samples.
Similar to Meaney and Szyf’s study, Moore’s study looked at differences in children based on whether they experienced high or low contact. They found differences in epigenetic markers between the two groups.
Children who experienced low contact at 5 weeks of age had epigenetic changes in 5 areas of the genome.
One of these areas codes for immune system functions that regulate T-cells. T-cells are involved in many autoimmune diseases, including type 1 diabetes. They are also altered in chronic fatigue (ME/CFS or myalgic encephalitis / chronic fatigue syndrome) (5)Jason, L. A., et al. (2009). “Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.” J Behav Neurosci Res 7(2): 1-17, (6)Craddock, T. J., et al. (2014). “A role for homeostatic drive in the perpetuation of complex chronic illness: Gulf War Illness and chronic fatigue syndrome.” PLoS One 9(1): e84839.
A second area of epigenetic change was seen in a gene that affects metabolism and 3 other areas have functions that aren’t yet known. The long-term downstream effects of these changes aren’t known either although other studies (including Tony Madrid’s as well as Meaney & Szyf’s) suggest they affect long-term health.
The authors found another set of changes in the epigenome of children who experienced low contact. This relates to a new field looking at “epigenetic age.”
Epigenetic changes in cells accumulate over the lifetime. This is at least in part due to our experiences. Epigenetic “age” can be assessed with blood and tissue samples and can accurately calculate chronological age. It is also an emerging and “robust” biomarker of health and disease in different populations (7)Chen, B. H., et al. (2016). “DNA methylation-based measures of biological age: meta-analysis predicting time to death.” Aging (Albany NY) 8(9): 1844-1865.
Moore’s team found that infants in the low contact groups had altered epigenetic ages compared to infants in the high contact group, whose epigenetic age was normal for their chronological ages.
Infants who had shown greater distress, such as crying more, had a “younger epigenetic age.”
Low contact infants who did not express distress showed “an older epigenetic age.” Both of these groups – more distressed and least distressed – were in the low contact groups.
In adults, older epigenetic age is associated with “greater morbidity, mortality, and experiences of psychological stress” Younger epigenetic age is also linked to health conditions (8)Moore, S. R., et al. (2017). “Epigenetic correlates of neonatal contact in humans.” Dev Psychopathol 29(5): 1517-1538.
While it is not yet known what these epigenetic ages mean in babies and children, the studies mentioned above (Chen, on wikipedia and cited by Moore) suggest it is a marker of health and reflects past exposures and events.
Moore and her colleagues speculate that younger “epigenetic age” in distressed low contact babies could indicate delays in developmental milestones.
They hypothesize that older or “accelerated” epigenetic in infants who did not express distress, however, could be indicators of resilience and decreased sensitivity:
Rather than infant distress marking sensitivity to high and low care, it is possible that those infants demonstrating the lowest levels of distress (which were all in the low contact group) are thriving with minimal care, whereas those infants high in distress are facing greater biological consequences in the face of low contact levels.
Given what we know about how perinatal stress triggers bonding disruptions and decreased contact in mothers, however, I have a different hypothesis.
The assessment of low distress as a sign of health and resilience could be accurate. It could instead be a false interpretation of an infant who is distressed beyond survival states of fight and flight, which involve protesting and calling for help, such as through crying. An infant in an environment of low contact who expresses no distress may be in the more deeply traumatized state of freeze, which is associated with futility, hopelessness and varying degrees of immobility. In this state, we no longer attempt to flee, struggle, or cry. This state of quiet detachment is seen as a danger signal in children who are hospitalized, to give one example.
One of the factors leading to long-term symptoms following trauma is that the event stimulates states of helplessness, loss of control or “freeze” (9)Scaer, R. (2005). The Trauma Spectrum: Hidden wounds and human resiliency. New York, W.W. Norton. This can occur very early in life, as described in the first and second posts of this series. Long-term effects of helplessness are also seen following adverse events in childhood (10)Shonkoff, J. P., et al. (2012). “The lifelong effects of early childhood adversity and toxic stress.” Pediatrics 129(1): e232-246. I will address the role of the “freeze” state in more detail in another post.
As I’ve introduced earlier and in previous posts, stressful events in very early life increase risk for chronic illnesses such as asthma and type 1 diabetes. One of the factors identified with this risk is that events in a woman’s life during pregnancy, birth and in her child’s early years affect her ability to bond, connect and make contact with her child. Specifically, the degree of contact, holding, gazing, and connection a mother has with her baby decreases when she experiences adverse events, and one of the reasons is that such events increase rates of maternal-infant separation (11)Klaus, M. H. and J. H. Kennell (1976). Maternal-infant bonding. St. Louis, Mosby, (12)Madrid, A. (2005). “Helping children with asthma by repairing maternal-infant bonding problems.” Am J Clin Hypn 48(3-4): 199-211.
Given these links, I wonder if deviations in epigenetic age indicate risk in both low contact groups, just as they do in adults. I wonder, based on the arguments presented by Moore and her colleagues, whether younger and older “epigenetic ages” are both markers for risk for chronic health conditions and / or indications of already existing developmental delays and other preclinical or early symptoms.
Ultimately, science helps explain how a mothers’ behaviors influences and shapes her child’s long-term health. Human behaviors and experiences, just as in animals, influence genes through the process of early bonding, attachment, and epigenetics. And more studies are emerging showing that maternal experiences of prenatal stress influence epigenetics in her children and affect genes related to immune system function, metabolism, stress responses and more (13)Cao-Lei, L., et al. (2015). “Pregnant women’s cognitive appraisal of a natural disaster affects DNA methylation in their children 13 years later: Project Ice Storm.” Transl Psychiatry 5: e515, (14)Cao-Lei, L., et al. (2016). “DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13(1/2) years: Project Ice Storm.” Clin Epigenetics 8: 54, (15)Veru, F., et al. (2015). “Prenatal maternal stress predicts reductions in CD4+ lymphocytes, increases in innate-derived cytokines, and a Th2 shift in adolescents: Project Ice Storm.” Physiol Behav 144: 137-145.
Reversal of epigenetic changes is possible and may very well be what happened when Tony Madrid helped mothers recover from adverse experiences that affected their well-being, their bonds with their babies, as well as their behaviors. It may also be why helping mothers heal can cure asthma in their children.
The new and emerging science is confirming what Hofer found when rat pups were separated from their dams and developed higher rates of increased blood pressure as adults (16)Hofer, M. A. (1981). “Toward a developmental basis for disease predisposition: the effects of early maternal separation on brain, behavior, and cardiovascular system.” Res Publ Assoc Res Nerv Ment Dis 59: 209-228, and what Dahlquist proposed when she noted that stress was the common denominator among risk factors for type 1 diabetes in pregnancy, birth and infancy (17)Dahlquist, G. and B. Kallen (1992). “Maternal-child blood group incompatability and other perinatal events increase the risk for early-onset type 1 (insulin-dependent) diabetes mellitus.” Diabetologia 35(7): 671-675.
What studies are confirming is that the effects of adverse environments on long-term health are not psychological. It’s because there are links between chronic disease, epigenetics and stress.
The Effects of Experience Can Last a Lifetime
Meaney and Szyf also learned that the protective effects of greater calm and decreased sensitivity to stress in more nurtured pups lasted throughout their lifetimes.
This was a result of epigenetic changes that continued throughout the lives of the pups.
Maternal Experiences Affect Generations
Last but not least, the researchers also discovered that a mother rat’s behavior, including the degree to which she nurtured her pups, influences genetic expression not only in her offspring but also in her offspring’s pups.
These epigenetic changes were passed on for generations.
You can learn about Meaney and Szyf’s story and work in a great article in Discover magazine called “Grandma’s Experiences Leave a Mark on Your Genes.” There’s more on epigenetics and chronic illness in a Nova documentary called The Ghost In Your Genes. And you can read about the influence of maternal behaviors on health and epigenetics in the book Epigenetics: The Ultimate Mystery of Inheritance (formerly called How Environment Shapes our Genes) (18)see Chapters 4 & 6 for discussions about the effects of maternal behaviors.
It turns out that this research is now widely known in many fields of study even though it is rarely recognized in clinical medicine and when taking histories of people with chronic illnesses.
Genes Are Affected During Sensitive Periods
Meaney, Szyf and colleagues made another discovery that was relevant to Tony’s work with asthmatic kids.
They found that dams’ behaviors altered epigenetics in their rat pups during a very specific period of time. These changes took place during the first week after birth.
This is an example of nurture (behavior) interacting with nature (genes) to affect physiology. It’s referred to as a sensitive or critical period.
The Sensitive Period After Birth
Mothers who see and hold their babies in the first hours after birth tend to bond more easily to their newborns. They are more nurturing with their babies and hold them longer, keep them closer and gaze at them more. As with rat pups raised by more nurturing mothers, these babies are calmer than infants whose mothers express fewer bonding behaviors as a result of separation and interruptions to bonding (more details in Part 2 of the series).
These calmer babies also cry less. Smile more. Their mothers experience more ease when they first try to breastfeed. And they tend to breastfeed for longer periods (months rather than weeks). As Tony Madrid and an increasing number of other researchers have discovered (19)Moore, E. R., et al. (2012). “Early skin-to-skin contact for mothers and their healthy newborn infants.” Cochrane Database Syst Rev(5): CD003519 , these babies are also easier to soothe, grow faster, get sick less often and experience many other benefits.
A sensitive period that supports maternal-infant bonding and more nurturing behaviors appears to be greatest during the first hour or two after birth (20)Bystrova, K., et al. (2009). “Early contact versus separation: effects on mother-infant interaction one year later.” Birth 36(2): 97-109, (21)Klaus, M. H. and J. H. Kennell (1976). Maternal-infant bonding. St. Louis, Mosby, (22)Klaus, M. H., et al. (1972). “Maternal attachment. Importance of the first post-partum days.” N Engl J Med 286(9): 460-463.
*Although most research has focused on mothers, studies also show that fathers fall in love and bond more easily with their babies when they get to spend more time with them in the first hours and days after birth too (23)Klaus, M. H. and J. H. Kennell (1976). Maternal-infant bonding. St. Louis, Mosby.
Supporting Moms: Supporting Generations
What we’ve been learning about epigenetics provides a powerful explanation for psychologist Tony Madrid’s work in healing asthmatic kids by treating their mothers for experiences that interfered with bonding.
When women heal from difficult or painful events that happened during their pregnancies, at birth and in the first 2 years of their asthmatic children’s lives – it changes how they feel about their children, makes them more nurturing towards their kids, and heals their asthma. It does so by reinstating an underlying capacity mothers have to love their children that were interrupted by difficult events that happened outside of their control (24)Madrid, A., et al. (2012). “The Mother and Child Reunion Bonding Therapy: The Four Part Repair.” Journal of Prenatal and Perinatal Psychology and Health 26(3) .
An additional support for Madrid’s treatment effects came from Meaney and Szyf’s finding that epigenetic modifications in less nurtured mice could be reversed. Even in adulthood. And it was evidenced when their skittish behaviors resolved after treatment (25)Weaver, I. C., et al. (2006). “Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood.” Proc Natl Acad Sci U S A 103(9): 3480-3485.
One of the fascinating and inspiring characteristics about how maternal behaviors influence epigenetics and perceptions of threat is that these epigenetically based changes can be reversed.
This research is pointing us in an entirely different direction regarding how to understand chronic diseases such as asthma.
This isn’t about bad mothers.
And it’s not just about the genes we inherit.
It’s about experiences that enable mothers to bond to their little ones when they are most vulnerable and have the greatest need for protection, safety, and care.
Experiences interact with genes during sensitive periods to meet the needs of the moment. This is how nature maximizes development and long-term adaptability as well as the chances of survival.
It’s also one way in which newborns develop subtle, cellular perceptions of threat from events occurring outside of their control. And even when they are not physically harmed or abused.
It occurs at the level of epigenetics.
These facts were nothing less than mind-bending when I discovered them.
They were also life-changing.
Chronic Disease, Epigenetics and Stress: Do Perinatal Events Affect Risk for Other Chronic Illnesses?
Epigenetics provides a remarkably different context for understanding the role of prenatal and perinatal risk factors for asthma. And for type 1 diabetes as well.
I wondered again whether events occurring during early life imparted risk for other kinds of chronic illness.
I was curious not only about my asthma but about my experiences of increasing fatigue as well.
And I was intrigued about the characteristics of “perceptions of threat.”
Tony suggested that healing my own experiences from prenatal life, my birth and surrounding my mother’s losses in my first few years might help treat my asthma.
I put it on my to do list. And I looked forward to seeing if it could also help my symptoms of fatigue that were eventually diagnosed as chronic fatigue syndrome (CFS).
Treatment and Research
In recent years Dr. Martha Welch a former student and collaborator of Dr. Myron Hofer’s (mentioned in the first post of this series) has implemented a program to support mothers and their premature babies. She is conducting this in a research study at Columbia University. The intervention is called the Family Nurture Program and was presented on PBS in May 2017 in Parts 1 and 2. The primary goal is to decrease risk for emotional and developmental disabilities by teaching mothers to interact with their premature babies in ways that support and calm the nervous system even while they are still in the intensive care unit (a huge impediment to bonding and co-regulation).
This is a hugely encouraging and validating step for the importance of these early life events.
Another is that it turns out there are approaches for helping adults heal the long-standing effects of difficult prenatal and perinatal experiences – both their own and their parents’. Even though these events happened decades in the past. Even when they involve perceptions of threat so subtle that there is no conscious awareness of their existence. Or of why perceptions of threat or lack of safety might exist in the first place.
I’ve had some in-depth experiences using therapies for healing trauma and working with my symptoms. It has made a big difference in my life, including what appears to be a complete resolution of my asthma. And gradual improvement of my CFS. I introduce this topic in my story.
When I started researching this information almost 20 years ago, I had questions that danced in my head like
sugar plums apple blossoms.
What if there weren’t uniquely different causes for each disease?
What if chronic diseases were caused by common types of risk factors?
I wondered what role perceptions of threat played in CFS and in other chronic illnesses, if any?
One area I focused on was to see whether similar perinatal risk factors existed for other chronic illnesses in addition to asthma and type 1 diabetes (there wasn’t much about ME/CFS at the time). If so, I wondered whether the information I’d learned would fit those findings. Or help make sense of studies with conflicting findings.
There’s more to come about the science that guided me to a new way of thinking in future posts.
What You Can Do
Here’s a list of therapies for working with different types of trauma and subtle perceptions of threat. They are also helpful for working with chronic illness.
Learn more about risk factors for chronic illness from pregnancy, birth and infancy in the first post of this series describing research in type 1 diabetes and in the second post on asthma. The tools for working with asthma have not been tested with other chronic illnesses that I know of but are still appropriate for healing PTSD and other symptoms linked to difficult experiences from early in life (whether you are a parent who had difficult experiences during the birth of your child or an adult with a chronic illness and a history of adverse events in early life). Based on the research I’ve done over the past 15 years, work with clients introducing these perspectives, and deep explorations of these insights in my own journey with ME/CFS and asthma, these approaches are also helpful for working with many types of chronic illnesses, health problems, as well as emotional symptoms and mental illness.
Leave a comment and let me know which of the risk factors or insights you resonate with the most.
Is it helpful to know about genes and how life experiences can influence our health?
Does it help make sense of your symptoms or chronic illness?
Does it offer relief? Or hope?
Let Me Know In a Comment
References [ + ]
|1.||↑||Madrid, A. (2010). The Mother and Child Reunion: Repairing the broken bond. Monte Rio, Lulu Press|
|2.||↑||Weaver, I. C., et al. (2004). “Epigenetic programming by maternal behavior.” Nat Neurosci 7(8): 847-854|
|3.||↑||Weaver, I. C., et al. (2004). “Epigenetic programming by maternal behavior.” Nat Neurosci 7(8): 847-854, p. 847|
|4, 8.||↑||Moore, S. R., et al. (2017). “Epigenetic correlates of neonatal contact in humans.” Dev Psychopathol 29(5): 1517-1538|
|5.||↑||Jason, L. A., et al. (2009). “Kindling and Oxidative Stress as Contributors to Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.” J Behav Neurosci Res 7(2): 1-17|
|6.||↑||Craddock, T. J., et al. (2014). “A role for homeostatic drive in the perpetuation of complex chronic illness: Gulf War Illness and chronic fatigue syndrome.” PLoS One 9(1): e84839|
|7.||↑||Chen, B. H., et al. (2016). “DNA methylation-based measures of biological age: meta-analysis predicting time to death.” Aging (Albany NY) 8(9): 1844-1865|
|9.||↑||Scaer, R. (2005). The Trauma Spectrum: Hidden wounds and human resiliency. New York, W.W. Norton|
|10.||↑||Shonkoff, J. P., et al. (2012). “The lifelong effects of early childhood adversity and toxic stress.” Pediatrics 129(1): e232-246|
|11.||↑||Klaus, M. H. and J. H. Kennell (1976). Maternal-infant bonding. St. Louis, Mosby|
|12.||↑||Madrid, A. (2005). “Helping children with asthma by repairing maternal-infant bonding problems.” Am J Clin Hypn 48(3-4): 199-211|
|13.||↑||Cao-Lei, L., et al. (2015). “Pregnant women’s cognitive appraisal of a natural disaster affects DNA methylation in their children 13 years later: Project Ice Storm.” Transl Psychiatry 5: e515|
|14.||↑||Cao-Lei, L., et al. (2016). “DNA methylation mediates the effect of exposure to prenatal maternal stress on cytokine production in children at age 13(1/2) years: Project Ice Storm.” Clin Epigenetics 8: 54|
|15.||↑||Veru, F., et al. (2015). “Prenatal maternal stress predicts reductions in CD4+ lymphocytes, increases in innate-derived cytokines, and a Th2 shift in adolescents: Project Ice Storm.” Physiol Behav 144: 137-145|
|16.||↑||Hofer, M. A. (1981). “Toward a developmental basis for disease predisposition: the effects of early maternal separation on brain, behavior, and cardiovascular system.” Res Publ Assoc Res Nerv Ment Dis 59: 209-228|
|17.||↑||Dahlquist, G. and B. Kallen (1992). “Maternal-child blood group incompatability and other perinatal events increase the risk for early-onset type 1 (insulin-dependent) diabetes mellitus.” Diabetologia 35(7): 671-675|
|18.||↑||see Chapters 4 & 6 for discussions about the effects of maternal behaviors|
|19.||↑||Moore, E. R., et al. (2012). “Early skin-to-skin contact for mothers and their healthy newborn infants.” Cochrane Database Syst Rev(5): CD003519|
|20.||↑||Bystrova, K., et al. (2009). “Early contact versus separation: effects on mother-infant interaction one year later.” Birth 36(2): 97-109|
|21, 23.||↑||Klaus, M. H. and J. H. Kennell (1976). Maternal-infant bonding. St. Louis, Mosby|
|22.||↑||Klaus, M. H., et al. (1972). “Maternal attachment. Importance of the first post-partum days.” N Engl J Med 286(9): 460-463|
|24.||↑||Madrid, A., et al. (2012). “The Mother and Child Reunion Bonding Therapy: The Four Part Repair.” Journal of Prenatal and Perinatal Psychology and Health 26(3)|
|25.||↑||Weaver, I. C., et al. (2006). “Maternal care effects on the hippocampal transcriptome and anxiety-mediated behaviors in the offspring that are reversible in adulthood.” Proc Natl Acad Sci U S A 103(9): 3480-3485|