Understanding Behavioral Epigenetics vs Increasing Access to Psychiatric Drugs for Children

These two topics could be two different blogs posts, but I decided to put them together because, in considering the larger question of where we invest our resources in promoting children's mental health, the two are subjects are linked. The first fills me with excitement and optimism, the second with despair.

My blog posts have been less frequent because I have been hard at work, under the guidance of the brilliant behavioral geneticist David Reiss, revising the section of my book that covers the critically important topic of epigenetics. Knowledge in this discipline is exploding, and he generously offered me the most up to date references. I am eager to see how this complex information translates for a general audience. Any comments to that effect will be much appreciated.

Epigenetics puts a whole new spin on the “nature vs. nurture” debate, which has historically viewed genes and environment as separate independent factors in determining the course of an individual’s development. Rare genetic disorders that result from a single change in the gene sequence have strengthened this misconception that one’s genetic makeup inevitably determines one’s future. Epigenetics refers to changes in DNA structure which alter gene expression, and hence individual characteristics, that do not involve changes to the sequence of DNA. According to leading researcher Michael Meaney, behavioral epigenetics specifically refers to the way environment, or life experience, influences gene expression and subsequent behavior and development.

The significance of this research for parenting is that that a child may be born with a particular gene for some problematic trait. But the effects of that gene on behavior will vary according to the environment. If parents do not respond negatively to difficult behavior, the effects of that gene may be altered and the problematic behavior may not occur. Conversely, negative response to challenging behavior will lead to expression of behavior associated with the problematic gene. These genes directly affect the development of the structure and biochemistry brain.

(For those readers who interpret this material as blaming parents when things go wrong, I refer you to an earlier blog post Guilt, Blame and Responsibility)

The importance of family environment on moderating genetic influence have been demonstrated widely in infants, children and adolescents. One particularly striking example is research on the (S) or short allele of the serotonin transporter gene . This gene is associated with stress responsivity and also with structure and function of the amygdala and medial prefrontal cortex, brain structures which are critical in emotional regulation. A person may have the short allele, but its expression, or its effect on behavior, is strongly affected by life experience. For example a person with the short allele has an increased risk of depression if he experiences stressful life events. Frances Champagne, a major figure in the field, writes in her paper, How social experiences influence the brain

Although these examples of interactions between genotypes and early environment are striking, we are only starting to fully appreciate the complex interplay between genetic backgrounds, social environments and brain development. Indeed, it is likely that such interactions[between genes and environment} will be found to be common and significant in development of most behavioral phenotypes[individual characteristics].

While hard at work wrapping my mind around these important research findings, I received, in AAP smartbriefs, a daily email about pediatric related news stories, an item about a recently published study in Pediatrics about a Massachusetts based program designed to improve access to child psychiatry services, known as MCPAP. Internal Medicine News sums up the study as follows;

A state-funded initiative to offer free mental health consultations to pediatric primary care physicians increased the proportion of pediatricians who said they were able to meet the needs of their psychiatric patients from 8% to 63% in 3.5 years.

Translation: Primary care doctors significantly increased their prescribing of psychiatric medication to children. In my opinion, this is not a statistic to be proud of. From 2005 to 2010 I was part a pediatric practice receiving the services of the MCPAP program. In May 2009 I heard Barry Sarvet, the lead author on the current study, speak at the 5th Annual Child Psychiatry in Primary Care Conference. At this conference he clearly and unequivocally supported the prescribing of psychoactive medication by pediatricians to young children, including atypical antipsychotics. Granted, this prescribing is under the guidance of a MCPAP psychiatrist. Some of these children are seen for a one time consultation, but in many cases the psychiatrist simply speaks with the pediatrician on the telephone.

In March of 2009 I wrote an op ed for the Boston Globe entitled Backed into a Treatment Corner. In the article I describe two very troubled patients for whom who I felt forced into prescribing psychiatric medication. I made the analogy to expecting a primary care clinican to treat a brain tumor.The article made no mention of the MCPAP program. It was widely praised, and many of the letters to the editor spoke to the importance of exposing this widespread problem. A few days after it was published,however, I received a call from Dr. Sarvet. He was furious. Apparently he had gotten in trouble with the powers that be that provide funding for MCPAP. My piece apparently made them look bad. I found this interesting, because in fact one of the patients was from New York State and thus not under the jurisdiction of MCPAP. Yet Dr. Sarvet experienced my piece as a condemnation of his program. When I explained that this had been far from my intention in writing the piece, his response was,"Well, its too late to take it back."

Certainly MCPAP was successful in accomplishing what it set out to do. My individual experience was that the participating psychiatrists were very helpful. They responded to my questions, which almost exclusively were about prescribing medication to older children with a diagnosis of ADHD, in a timely manner. But read the fine print in the current Pediatrics article:

FINANCIAL DISCLOSURE: Dr Prince serves as a consultant to
Astra-Zeneca, is a member of the speakers bureau for McNeil
Pharmaceutical, and has received a speaker’s honorarium from
Shire, and Dr Bostic serves as a consultant to Forest
Laboratories and GlaxoSmithKline; the other authors have
indicated they have no financial relationships relevant to this
article to disclose.

I can't help but wonder if all of the MCPAP psychiatrists have at some point in their career,if not specifically in relation to this article, had significant associations with the pharmaceutical companies who profit from prescribing of psychiatric medication to children. Has this relationship affected their recommendations regarding prescribing practices? I am hard pressed to believe that it has not.

So how to fit these two seemingly disparate topics together? Rather than channelling money into programs that increase use of psychiatric medication for young children, wouldn't it make more sense to turn our attention to prevention, and to supporting families in promoting children's healthy emotional development? If the research in epigenetics is showing that with such interventions we might actually impact on gene expression, and in turn grow and development of the brain, this seems a far better path to pursue than changing young developing brains with powerful psychiatric medications.

If health care providers on the front lines have the time to develop relationships with young families, if there is a strong system of mental health care to support families who are struggling, and a medical education system that supports clinicians in their efforts to listen to parent’s stories, we will be well on our way. The image comes to mind of a set of Russian dolls. The highly valued primary care clinician, reimbursed by the health care system, listening to the whole of parent’s experience, can help bring out their basic wisdom and inherent intuition. Then we as a society could be said to be holding all children in mind.

High Tech Baby Monitors Prey on Parent's Vulnerabilities

Recently I was interviewed by a reporter about the effects of the newest baby monitors on parent-child relationships. A teddy bear with a camera in its nose hooks up to a TV, allowing parents to watch their baby's every move. One product called an exmobaby is actually worn against the baby's skin and measures heart rate and respirations. A CEO of the company is quoted a saying, presumably as a selling point, “This continuous monitoring in realtime will allow for an ‘emotional umbilical cord’ between mother and child.” My conversation with this reporter got me thinking.

When we become parents we have the opportunity to open our hearts to a love unlike any other. This love may begin at the moment a mother learns she is pregnant. But in opening ourselves to this love, we take a risk. Though the idea is mostly out of our conscious awareness, in becoming parents we make ourselves vulnerable to an unlikely but real possibility of unbearable loss.

A central task of parenting is to manage our anxiety around this possibility. Not only when we put our children to bed, but when we let them go down a slide, go to preschool, go skiing in Europe. We allow them to separate and grow up. All along we must learn to manage our anxiety.

When I was pregnant with my son, we were told that he might have a very serious heart condition. He was followed with yearly tests and then last spring, when he was 12, we were told that he and his heart had grown to the point where the doctors felt we didn't need to worry about it. Even now, every night when I say "Goodnight, I love you, see you in the morning," I remember the gripping fear of loss. But when at the age of eight he begged to go to sleep away camp like his big sister, we let him go.

Now along come these baby monitors which, in my opinion, abuse this vulnerability for profit. Certainly if a baby has an identified medical condition, monitoring of heart rate and respirations may be indicated. But these monitors need to be used carefully and under supervision of a health care provider. For a baby who has no such identified risk, there is no reason to monitor him. Putting a child under the age of six months to sleep on his back does more to protect him than any baby monitor ever could. A simple audio monitor that allows parents to hear a baby if he cries during the night many be helpful. But unless you have a huge house, or are having a party, you will generally be able to hear your baby's cry during the night, and even that may not be necessary.

Another drawback of these monitors is that they send parents a message that it is not OK to leave your baby to do adult activities. What about watching a movie instead of your baby on TV? I read a recent blog post with the title"Attachment Parenting-Is It a Prison for Moms? "Attachment parenting is a style of parenting described by William Sears that advocates for a mother to be with her child as much as possible, including carrying and cosleeping. (It is distinct from and unrelated to John Bowlby's attachment theory.) These are fine choices if parents wish to make them. But it is important to recognize that solid relationship between parents, one that is often fostered by having adult time together, can contribute significantly to a child's healthy emotional development. It helps both parents and child negotiate the challenging task of separation.

As I approach the age of 50, I am aware that I need to work hard to be open minded to new technologies. But to high tech baby monitors, I give it an unequivocal thumbs down.

Diagnosing Autism in Infancy?

Two juxtaposed slides presented at a talk by William Singletary on autism at last years annual American Psychoanalytic Association's meetings capture, in my opinion, the essence of the disorder. In one, a baby is held in the soft embrace of mother's arms, gazing back into her adoring face. In another, a baby screams as he looks into the wide open mouth of a fang bearing snake. These photographs vividly demonstrate that these children experience the world not as as soft and loving, but rather as harsh and frightening.

When the gene for autism is finally discovered, I believe it will be closely linked to the processing of sensory input. While non-autistic newborns experience touch and a loving face as comforting, autistic children are overwhelmed, and so retreat to the world of inanimate objects.

A New York Times article this past week At the Age of Peekaboo, in Therapy to Fight Autism describes current research into diagnosis and treatment in infancy, using an intervention based on the Early Start Denver Model. I referred to this intervention in my Boston Globe op ed about the limits of medication in treatment of autism.

An intervention, the Early Start Denver Model, was offered in the homes of families, with parent, child, and therapist playing together. In the two-year study period, toddlers diagnosed with autism showed significant improvement in behavior, language, and IQ. The authors attribute the success of their intervention to the fact that it is “delivered within an affectively rich, relationship-focused context.’’

While I have some concerns about diagnosing autism in infancy (more about that below) I feel strongly that a relationship based intervention is the way to go. If I am correct, and the primary problem lies in the way an infant experiences his environment,it is a quality with which he enters the world. But immediately after birth, this genetic vulnerability begins to wreak havoc on the environment.

Holding, feeding, comforting-these are the actions that give a new mother not only pleasure, but growing confidence in her mothering capacities. When she fails at even one of these, such as with a spitty baby who has difficulty tolerating feeds, a sense of inadequacy can follow. But if you multiply that to cover all the senses-if being held is not comforting, if singing provokes screaming,smiles are too much, that inadequacy can be devastating. Mothers may become depressed. Marriages are severely strained. Siblings may be neglected, become resentful and act out. For these reasons, it is essential that from the very beginning these problems are treated in the context of relationships.

Another study published this past week described in a Reuters article Autism risk gene may rewire brain looks at the brains of children with autism using functional MRI.

The team measured the strength of brain connections as the children worked. They found children with the version of the gene linked with autism called contactin associated protein-like 2 or CNTNAP2 had strong brain connections within the frontal lobe, but weaker connections to the rest of the brain."In children who carry the risk gene, the front of the brain appears to talk mostly with itself," Ashley Scott-Van Zeeland, now at Scripps Translational Science Institute, said in a statement.

In a previous blog post, I have describe the way in which early mother infant interactions wire the brain.

When a parent gazes into her baby’s eyes, she literally promotes the growth of her baby’s brain, helping it to be wired for a secure sense of self. The medial prefrontal cortex(MPC) has been referred to as the “observing brain.” It is where our sense of self lies. When a mother looks at a baby in a way that communicates with him, not with words but with feelings, “I understand you,” he begins to recognize himself, both physically and psychologically. This mutual gaze, literally and figuratively being “seen,” actually facilitates the development of the baby’s brain. As the MPC matures in this kind of secure loving relationship, the brain is wired in a way that will serve him well for the rest of his life. He will be able to think clearly and to regulate feelings in the face of stressful experiences.

It makes perfect sense that if this mutual gaze process goes awry from the start, the projections from the frontal lobe to the rest of the brain would not develop properly. Again this leads back to the critical importance of relationship based treatments.

All of which leads to my concern with the labeling of young infants with a devastating psychiatric disorder. I wish there were a way to recognize the infant's experience of the world, and to support parents efforts to interact with their infants in a way that reflects this understanding, without pathologizing it from the start. This would mean acknowledging that there is something different about these children that makes caring for them extremely challenging. It would mean offering services to families, such as the Early Start Denver Model, but without necessarily labeling infants as autistic.

Some parents may find comfort in a label. It demystifies their difficulties and relieves alot of the guilt and sense of inadequacy. But there is a process of mourning that goes along with receiving such a label and may affect the way parents see their child for the rest of his life. Also there is a risk that the family context of the problem is overlooked when the problem is seen as residing exclusively in the child.

I don't have an easy answer for this dilemma. But these news stories have motivated me to put the ideas out there, and I hope start a discussion about these challenging questions. Of one thing I am certain. The answer lies in continuing to devote resources to identifying these problems early, and supporting early parent-child relationships, with the long term goal of facilitating the healthy emotional development of the next generation.

Ode to Grandmothers

Last week, a friend told me a story that motivated me to recognize the important role of grandmothers, not specifically for their grandchildren, but for their adult daughters who are now mothers.

My friend, mother to a fifteen year old boy in the throes of adolescent turmoil, did not have a close relationship with her mother when her children were young. Her mother preferred "not to meddle," despite her daughter's clear requests for her involvement. My friend struggled with this for years, seeking help and support from others, particularly her husband and close friends. Still she very much longed to connect with her mother. So she continued into her forties to put a lot of effort into this relationship. The other day, she told me, the effort seemed to have paid off.

She was having a particularly bad moment with her son, who chose an afternoon when she was feeling tired and stressed by her own work, to regale her with all of her faults and accuse her of being the cause of all his misery. The more she tried to talk to him, the more the conversation degenerated, to the point where she couldn't stand it anymore and got in her car and drove off. Much to her surprise, she found herself driving to her parents house, something she never spontaneously did, despite the fact that they lived close by.

Both her mother and father were overjoyed at her unexpected appearance. They made her tea and listened while she unloaded her distress. Then her mother, in a most uncharacteristic way said to her, "I know I might not have done all the right things when you were a kid, but I do remember that sometimes the only option was to keep a sense of humor."

My friend, who had been so caught up in her conflict with her son, suddenly saw that she had been fighting with him like she herself was a teenager. In the heat of the moment she forgot, though at saner moments certainly knew well, that teenagers are at times incapable of rational discussion. But until her mother heard her and reflected back what was happening, she had been unable to see it herself.

Dan Stern, in his book The Motherhood Constellation that outlines the basic principles of parent-infant psychotherapy, refers to the “good grandmother transference” to describe the kind of relationship a parent develops with the therapist who is working with a parent and child together. Transference is a psychoanalytic term that refers to the way people tend to transfer feelings from one relationship, often from childhood, to another current relationship. He writes:

The transference that evolves in this situation involves a desire to be valued, supported, aided,taught, and appreciated by a maternal figure.This desire for such a maternal figure is evidenced in many situations outside of the therapeutic one. Beginning in the hospital with the birth of the baby, mothers frequently find someone to fill this role or part of it. It is often a nurse, a nurses aide, the cleaning lady, or someone else who takes a moment to share personal experience and give heartfelt encouragement. It is amazing how important these short encounters can be. They are overwhelmingly with other mothers more experienced in motherhood...Later other mothers met in the park may fill this role, to say nothing of the mother's actual mother, grandmother, older sisters, and experienced friends.

Berry Brazelton, in his book Touchpoints: Birth to Three, in the section devoted to grandparents writes:

The best thing that has happened to me as a grandparent has been the chance for my children and me to have a whole new relationship...Each grandchild is a miracle, but a new relationship with your own children is an even greater one.

My forthcoming book, now in the final editing stages, speaks to the importance of supporting parents' efforts to be fully emotionally available for their children. Many of the mothers I describe in the book, mothers who have come to see me in my pediatric practice because of struggles with their children, have strained relationships with their own mothers. In effect they develop a kind of "good grandmother transference" with me. This is often very helpful to them in the task of raising their children. Though perhaps not within the scope of my role as pediatrician, I certainly wish for these mothers, and support them in any way I can, that they find peace, as my friend seems to have achieved, with their own mothers.