The Meadows Blog

Monday, 17 June 2013 20:00

Of Mice and Mothers: The Quality of Maternal Care Shapes Offspring Development

Jon Caldwell Jon Caldwell

It may surprise you to learn that some of the most compelling information we have about human attachment behavior comes from...rodents. That's right - like humans, these little mammalian mothers form attachment-like bonds with their young pups (i.e., rodent infants). As it turns out, the nature of this bond has a profound impact on the pup's development. It has become increasingly clear that the quality of the mother's care induces numerous biological changes in the pup that can be carried forward into adulthood and into the next generation. In fact, thanks to our furry little friends, we now understand some of the mechanisms involved.

Attachment theory, pioneered by John Bowlby and Mary Ainsworth in the early 1900's, put forth the idea that the bond between child and caregiver has been naturally selected for by evolution because it offers survival and reproductive advantages. Through a series of ground-breaking studies, they showed that children who are separated from their caregivers experience predictable stages of protest, despair and detachment. Subsequent attachment researchers, like Alan Sroufe, postulated that early attachment relationships organize the child's inner world, making them more or less able to negotiate future developmental challenges in middle childhood, adolescence and adulthood.

By the end of the twentieth century, attachment theory had risen to prominence in the field of psychology. Yet, little was known about the actual biological mechanisms responsible for most of its basic tenets. That began to change with fascinating research in mice and rats, like that of Marion Hofer and his colleagues. They recognized that, like human infants, rat pups experienced similar stages of protest and despair when separated from their caregiver. More importantly, they found that caregiver separation during specific periods of development (usually in the first two weeks) resulted in a number of physiological deficits in the rat pups.

In fact, Hofer and his colleagues discovered that during critical periods, specific maternal caregiving behaviors were related to the development of specific biophysiological processes in the rat pups.  For example, if pups were not allowed to receive body-to-body warmth and closeness from their caregiver, they developed specific deficits in their ability to regulate their activity level (e.g., they were more lethargic, hypoaroused). On the other hand, if the pups received caregiver warmth but did not receive a continuous infusion of maternal milk, then the pups were not able to regulate their heart-rate (but their activity level was normal). These researchers concluded that the caregiver-infant relationship contained within it "hidden regulators" that shaped the biophysiology of the infant in very fundamental ways.

Around the turn of the twenty-first century, there was incredible excitement about the promise of the human (and rodent) genome project.  Gradually, it became clear that simple one-gene-to-one-disease models were overly simplistic and that most conditions were a product of complex interactions between genes and the environment.

With this in mind, researchers like Michael Meaney extended the work of Hofer and others into a new dimension of research involving epigenetics.  Epigenetics refers to the somewhat radical idea that while our inherited genetic code remains fairly stable throughout the lifespan, the quantity and quality of protein products that are made from the genetic code are highly variable and are heavily influenced by the environment.  That is to say, the expression of the genetic code (i.e., which genes are turned on/off, in which parts of the body, at what times) is influenced by various environmental factors.

Michael Meaney's elegant line of research was kick-started by a simple laboratory observation that rat pups handled by humans tended to develop into less anxious and less fearful adults. Fortunately, they overcame the species-centric urge to attribute the positive results to human contact and discovered that pups that were handled by humans received more grooming from their mother. (Rat mothers were dutifully cleansing their pups of the human contact!) This led to the exciting discovery that it was the maternal rat's licking and grooming behavior that was responsible for their well-adjusted offspring.

Meaney and his colleagues found that high-quality maternal care in rats involves licking and grooming behavior and a style of nursing where the mother's back is highly arched. They also discovered natural variation in the quality of maternal care - some maternal rats were quite good at arched-back nursing and licking/grooming behavior, while others were not. This led to the discovery that pups who received high levels of maternal care (arched-back nursing and licking/grooming) were less anxious as adults, more willing to explore their environment and they became mothers who delivered high levels of maternal care to their own offspring.

Of note, these researchers wanted to be sure that the outcomes associated with high-quality maternal care were not simply due to inherited genes. So, they took pups from low-quality caregiving mothers and gave them to high-quality caregiving mothers (cross-fostering), and vice versa. The results showed that it was the quality of caregiving that determined the positive outcomes, not the pup's genetics.

Now these researchers had an animal model that looked a lot like what we see in humans: high-quality maternal care (i.e., attachment security) organizes developmental processes in a way that supports greater well-being and caregiving advantages for the subsequent generation. These researchers were perfectly poised to answer the next burning question: What are the underlying biological mechanisms?

This is where epigenetics re-enters the story! Meaney and his colleagues discovered that during sensitive periods of development (the first week of life for rats), high-quality maternal care actually stimulates (i.e., turns on) the expression of a gene that codes for a protein called glucocorticoid receptor (GR). In fact, the GR gene becomes more active because the mother’s licking and grooming behavior sets in motion a cascade of chemical messengers in the pup that eventually act on specific epigenetic factors (e.g., histones and methyl groups) that alter the shape of the DNA, making it more accessible for genetic expression.

As is common in epigenetics, the maternal rat's high-quality caregiving behavior stimulates GR gene expression in the pup at specific locations within the body: in this case, a brain region called the hippocampus. This is critically important because the hippocampus is involved in generating the body's fight or flight reaction to stress. When there are more glucocorticoid receptors present in the hippocampus, the fight/flight response is attenuated. Therefore, high-quality maternal care alters the shape of the GR gene, which leads to an increase in GR gene expression and an increase of glucocorticoid receptors in the pup's hippocampus. This results in a rat pup with better nervous system regulation that behaves more calmly and confidently as an adult.

Although epigenetic programming by maternal care occurs during sensitive periods early in life and tends to be stable over the lifespan, there is evidence that these effects can be reversed. Even as adults, these same epigenetic processes remain open to environmental influences and can potentially be harnessed for the purpose of change. There is some evidence that consistent and repetitive activation of certain brain circuits might induce epigenetic modifications, leading to stable changes in gene expression. Ultimately, changes in gene expression modulate complicated neurochemical feedback loops, which then alter the structure and function of neurobiological systems.

Thus, there is the real possibility that future research will help identify ways that specific environmental factors, including the environment of our own mind, can be utilized to gain access to these powerful epigenetic processes. In that wonderfully hopeful time, we will probably still be talking about mice and mothers.

Jon G. Caldwell, D.O., is a board certified psychiatrist who specializes in the treatment of adults with relational trauma histories and addictive behaviors. Dr. Caldwell currently works full-time as a psychiatrist at The Meadows treatment center in Wickenburg, Arizona. For many years he has been teaching students, interns, residents, and professionals in medicine and mental health about how childhood adversity influences health and wellbeing. His theoretical perspective is heavily influenced by his PhD graduate work at the University of California at Davis where he has been researching how early childhood maltreatment and insecure attachment relationships affect cognitive, emotional, and social functioning later in life. Dr. Caldwell's clinical approach has become increasingly flavored by the timeless teachings of the contemplative traditions and the practice of mindfulness meditation.

Read 5791 times Last modified on Thursday, 05 September 2013 10:38

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