Personal Reflections from Jarrett Barnhill, M.D.
In spite of nearly 25 years of struggling to understand and treat people with autism, I still have some nagging questions:
1.What is autism?
2.Do recent scientific discoveries offer hope or add to our confusion?
3.Why do we (Homo sapiens) have autism?
4.Can we do anything more than treat symptoms?
5.Have we forgotten about the human face of autism?
What is autism?
At its core, autism is a developmental disorder that affects fundamental brain processes associated with emotional attachment behaviors, social relatedness, communication, and adaptability. The level of intellectual disability and executive function deficits, as well as comorbid metabolic and neuro-psychiatric conditions, affect the severity of autism. The clinical diagnosis of autism is based on observable behaviors and not any specific medical or neurological test-that includes MRI, fMRI, PET, MRS, and EEG. To date there is no specific metabolic test, or single gene responsible for autism.
Although recent diagnostic criteria emphasize the age of onset, the age of recognition may be more clinically relevant. In fact, there may be a considerable discrepancy between the actual age of onset and that of recognition due to variability in the severity of intellectual disability and autistic symptoms (aloof, passive, active but odd, HFA) as well as the capacity of families or health care providers to recognize core symptoms. The age of recognition may also have a significant impact on the timing of and the types of intervention. As in many developmental disorders, early intervention programs may have the greatest impact on subsequent development. Unfortunately access to these resources is subject to larger social-cultural issues-budgets, ideologies, social attitudes, and the political process.
Our understanding of autism is still a work in progress. Early in my training, psychoanalytic armchair speculation dominated the study of autism. The etiology of autism was based on theories that pointed icy fingers at parents in general and mothers in particular. By the time I began my residency in child psychiatry at UNC-Chapel Hill in 1977, there was a different viewpoint. I had the good fortune of attaching myself to TEACCH for most of a year. Part of this learning focused on what Lee Marcus called "babysitting"- I sat with the kids during parent interpretive conferences. In spite of my ineptness, I carried away a deep appreciation of the complexity and individuality of people with autism as well as a healthy respect for a wide range of interventions. I still keep these experiences in mind, even though my career has focused on the neurobiology and neuropharmacology.
Do Recent Scientific Discoveries Offer Hope or Add to Our Confusion?
Fortunately, scientific empiricism and research have replaced the armchair speculations. We are in the midst of an era devoted to the scientific study of autism. Statisticians, neuro-chemists, neuro-imagers, and molecular geneticists replace the psychoanalyst. Even though we possess an enormous amount of scientific data, there are still many gaps between our knowledge and understanding. We can observe neuro-cognitive functions with fMRI, PET, and other marvelous scientific techniques. These studies provide clues about how the brain functions in autism. Neuropathologists are providing intriguing information about problems with nerve cell migration, differentiation, and intercellular communication. Neuro-pharmacologists can point to a wide range of neurotransmitter and neuro-peptide anomalies that are present in individuals with autism. Geneticists can address larger issues of inheritance while molecular geneticists address subtle abnormalities among chromosome or DNA transcription. Electrophysiologists are also looking into signaling abnormalities and problems with integrating and organizing input.
Do Recent Scientific Discoveries offer hope or add to our confusion- ontogeny?
Are people with autism born or made? The psychoanalytic models focused on "making" autism and did more damage than good. From another perspective, there are multiple neurological and metabolic disorders as well as primate models (early ablation studies) that produce autistic like behaviors. But there are also significant differences. There appears to be a critical period during development that results in what we call autism. Neurological disorders emerging during adult life differ from those present during brain growth and subsequent early development. It is difficult to create brain disorders that produce autism during adulthood.
Much of our modern developmental research focuses on the search for genes that play a key role in the inherited forms of autism. But how do genes affect complex human behaviors? Autism seems to be the result of early changes that may put cells in the wrong place at the wrong time, or fail to differentiate, or interconnect with other nerve cells. Part of this unfolding involves an increasing hierarchical organization and connection between multiple brain sites. This early organization is driven by a host of chemicals that turn genes on and off, attract neurons, and signal it is time to go to work, or die-some will become later hormones and neurotransmitters.
Brain development is vulnerable to a wide range of potential insults but these developmental abnormalities are modifiable. Although large-scale changes occur more during early childhood, the human brain is nearly continually changing and re-organizing. Brain structure and function do change throughout our lives and are sensitive to corrective experiences. But the earlier the intervention the better. So we must look at brain development and understand the role of plasticity within the human nervous system.
Plasticity also leaves room for experience-driven changes in both the structure and function within the central nervous system. Because of this malleability, early intervention programs may offer our greatest hope. Getting an early start may help people with autism compensate and develop alternative processes of learning, socialization, and communication.
In this sense genes are not laws carved into stone tablets. They are more like a blueprint, a guide to the finished product but there is ample room for many modifications- think of building a house, dealing with contractors, and little variations in the plans, and corrections to mistakes.
Why Do We Have Autism- Phylogeny?
Why are humans affected by autism? Where does autism fit into our evolution? It appears that autism is a truly unique human experience. But the definition of human-ness has become murkier with each new discovery from paleo- anthropologists and primatologists. But several things are apparent. We are compulsive communicators who are wired with an elaborate system for verbal and nonverbal communication. Our brain is organized to allow for speech and reciprocal communication with a wide range of conspecifics. We are also an adaptable species who survived and evolved during times of immense geological and climatic change. We are a highly curious species whose flexibility and complex learning allowed us to adapt to a wide range of econiches. We are a social primate with highly evolved cultures, social networks, and a dangerous capacity for tool making. We live in a world of ideas, religious beliefs, art, and creativity- very recent developments in evolutionary terms.
The human brain represents an extension of an older primate model with significant modifications. The first obvious differences is size; the second is re-ordering and redistribution of function to accommodate language and more complex cognitive abilities (prefrontal cortex). The driving force behind this dramatic neurological evolution was probably based on increased demands for communication and complex social skills- we didn't evolve to do calculus or read Shakespeare. When teenagers tell us that they are going to high school to socialize, they are reflecting our true heritage as compulsive communicators and socializers.
So why autism? Geneticists are focusing on genes that are involved in communication, social anxiety, behavioral flexibility, and complex brain functions. It is apparent from these studies that autism requires multiple genetic problems that underlie the core features of our species. Since these genes may have also evolved relatively rapidly, we might be able to recognize our ancestors 2-3 million years ago. We would probably not be able to find or recognize autism at that point either. Perhaps autism is the byproduct of our later evolution, and affects core features of our human-ness. Perhaps without autism we might not be Homo sapiens.
What are we treating?
In spite of countless "cures" over the past few decades, clinicians still struggle with aggression, SIB, stereotypies and ritualistic behaviors, hyperactivity, and social aloofness, as well as comorbid neuropsychiatric disorders. There is considerable heterogeneity in autism and significant variability in the frequency and severity of these target behaviors. Some of this variability comes from changing ecological circumstances, baseline exaggerations secondary to comorbid neuropsychiatric disorders, or both. As a result, a careful assessment includes a functional behavioral analysis, but also a careful review of temperamental and genetic risk factors, as well as medical, neurological and psychiatric assessments. Unfortunately there is considerable variability in interest and skill levels among medical, neurological, and psychiatric clinicians.
There is a great deal of "barnyard psychopharmacology" out there. Some of it is based on advertisements, anecdotes, and borrowing treatments from other psychiatric disorders. The rest may be best on the premature application of information about neurotransmitters, peptides, and enzyme activity. We need to be cautious about becoming overconfident that affecting serotonin, dopamine, secretin, endorphins, or pyridoxine as co-factors for enzymes will actually treat autism. Are we recreating a new generation of biological determinists? Are genes, neurotransmitters, and neuroimaging studies a modern version of previously discredited psychoanalytic notions about the CAUSE of autism? There is a danger of new biological determinism in which neurotransmitters replace mothers as the cause of autism.
The scientific study of treatment effectiveness requires a search for possible etiologies followed by careful measures of treatment responses. This methodology allows for a thoughtful integration of both subjective and objective treatment responses. Objective responses are frequently measured by rating scales that assign numbers and allow us to quantify clinical observations. Unfortunately ratings scales rely on observation and we should never assume that these values are any better than the raters.
We are entering a brave new world of evidence-based medicine (EBM). In this model, the reliability of evidence is rated based on the objectivity and hopefully reproducibility of treatment approaches. The most reliable are controlled studies followed by expert opinions or anecdotal, case reports. The best evidence for any given treatment involves well-designed double-blinded, randomized, and placebo-controlled or "head-to-head" comparisons between a new drug and established treatments. Sample size and power, types of statistical analyses add rigor but may detract from clinical reality-a 25% reduction in target symptoms may be statistically significant but clinically meaningless. Our reliance on scientific analysis can become an obsession as we wander aimlessly in a statistical Jurassic Park.
EBM is also inherently conservative. Evidenced-based medicine centers on pre-established methodologies but many zealous practitioners may tend to undervalue strategies that evolved from intuitive leaps or novel ideas. But without curiosity and sometimes desperation, there might be few new innovations. Unfortunately, there is frequently a schism between the innovators (or alchemists) and the priest of the scientific methodology, but this conflict is nothing new-this sort of dialectic has been the driving force for scientific discovery for many centuries.
The speed of information dissemination-including bad information-commonly outpaces controlled studies. New therapies emerge overnight over the Internet and inflame the hopes of parents and clinicians alike. But we are getting smarter and are a little better at recognizing treatable disorders-some metabolic disorders such as PKU and some forms of epileptic encephalopathies such Kleffner Landau Syndrome. But because autism is a heterogeneous disorder no single treatment will probably ever fit all. One of the more frustrating problems over the past three decades is the sensationalization of a "cure" followed by clinical experience and empirical data that deflates the original optimism. The most recent issues involve Hg/MMR, DMG, THC, magnesium/pyridoxine/niacin, secretin, and now risperidone (NEJM). Unfortunately many metabolic disorders lack cures and treatments are palliative at best.
Have we forgotten about the Human Face of Autism?
The neurosciences have limitations. We still struggle with the human face of autism in spite of our knowledge of brain nerve growth factors, cellular adhesion molecules, oxytocin, gastrin related peptides, serotonin receptors and transporter proteins, immunological mechanisms, genes and chromosomes. The role of science is the search for underlying mechanisms but in our zeal to discover we should not forget the larger experience of autism and the impact of this developmental disorder on affected individuals and their families.
As clinicians, we struggle to accept the limitations of our current treatments. Like parents and families, we use what we have while we wait for better tools in the future. Unfortunately the treatment of people with autism is littered with the corpses of once promising cures. It is often difficult to avoid professional cynicism while struggling to maintain the spark of hope of families. Both of us need to temper the peaks of promised cures and the valleys of despair and hopelessness when a much-ballyhooed treatment turns belly up.
Like families, clinicians also need to find a way to realistically accept our treatment limitations. I struggle with a small fraction of what parents and families face but still have to painfully accept that my best outcomes are modest at best. But the struggle goes on. Parents can struggle with me over this realization, and either search in desperation for others with "the answer," or struggle against despair. At this point they are probably most vulnerable to every new cure. Somewhere in this process, I usually find myself mentally reciting the "Serenity Prayer" written by Niehbur and adopted by Alcoholics Anonymous-- "God grant me the serenity to change the things that I can, accept the things that I cannot, and the wisdom to know the difference."
For most families something changes somewhere amidst this struggle. Part of this change comes from the realization that we are not only ones learning to cope with autism. Even though we continually struggle to understand autism, the person with autism also grapples to understand us. I have learned a great deal from this realization, but still have to constantly remind myself that the person with autism is also struggling mightily to make sense of me. My part of this journey mainly focuses on psychopharmacology--that's the easy part. Families struggle with lost dreams of the perfect children until at some point, they discover another unexplored country-the joy of the little events, small steps, and humorous moments. At this point, there is a clearly spiritual change that will forever defy scientific study-the pain wanes in power and a new sense of living waxes in importance.
Gandolf the Gray in "The Fellowship of the Ring" captures this change when he remarks to a despairing Frodo: "Its not the times we live in, that is important but how we use the time, we are given." Perhaps this is the cure for autism, not from a pill, protein, or behavioral technique but from far older human strengths-faith, hope, curiosity, and above all, tenacity.
Contact information: Jarrett.Barnhill@css.unc.edu.