This Is Your Brain On ADHD, Part III: Heredity, Environment & Beyond

The first two parts of this blog looked at brain research that seeks to explain ADHD, focusing on studies that have identified deficiencies in the dopamine pathway and those that have found differences in other parts of the brain. Part III briefly summarizes two additional research streams.These aim not at describing anomalies in the ADHD brain but at explaining their origins. One stream has associated them with genetic variations while the other has identified early childhood environmental factors that appear to present an increased risk for ADHD.

Since the 1980s there have been multiple demographic studies of the ADHD population. They have repeatedly demonstrated that if an individual has been diagnosed with ADHD, there is a 75-80% likelihood that at least one of their grandparents, parents, siblings, or children also meet the diagnostic criteria. Among identical twins the concordance jumps to 90%. This evidence persuasively suggests that ADHD runs in families – in other words, that in the great majority of ADHD cases, its source is in our genes.

Based on studies to date, scientists speculate that ADHD is probably associated with alleles, variant forms of a gene’s molecular structure that may cause atypical traits to occur. The largest body of evidence supports the dopamine hypothesis with studies citing alleles of two, four, or more genes that turn out to be common among ADHD people and appear connected with the dopamine deficiencies discussed in Parts I and II. Several other genes and alleles appear to be associated with the production and processing of glutamate, a neurotransmitter that influences the brain’s ability to control impulses. Genetic research has also identified an allele often found in ADHD people who have experienced positive outcomes with medication.

Some researchers hypothesize that three different constellations of alleles may account for the three presentations of ADHD currently diagnosed: primarily inattentive, primarily impulsive, and combined. There is also a growing consensus that ADHD may be heterogeneous in nature. This would mean that, rather than being a single condition, it is actually multiple conditions that derive from different genetic influences but, because their symptoms appear similar, have been classified as the same.

If 75-80% of ADHD cases derive from genes, what lies behind the other 20-25%? Public health studies have suggested that these may arise instead from environmental risk factors that are present during early childhood. Several of these – including the mother’s age at the child’s birth, her prenatal use of drugs, the family’s socioeconomic status, and a parental history of Conduct Disorder – each appear to increase the risk of ADHD by about 1%. A child’s in utero exposure to alcohol or to nicotine elevates the risk into the 2% range while low birth weight raises it to about 3%.

There is yet another environmental factor that presents a much greater and more disturbing statistical risk than any of those mentioned above. This is the potential damage associated with trauma that occurs during the first few years of life and results when children are exposed to one or more of several adverse experiences: physical abuse, sexual abuse, domestic violence, extreme neglect, parental abandonment, multiple foster placements, or the suboptimal care provided by many offshore orphanages where hundreds of thousands of adopted American young people were “housed” during infancy.

All these conditions may profoundly disrupt children’s attachments with their primary caregivers, producing extreme levels of fear and stress that can have a significantly negative impact on how fully and normally their brains become “wired.” The result can be a disruption in neural integration (connection and communication between brain parts) that leads to difficulty with multiple facets of self-regulation. These include problems controlling anger, aggression, anxiety, distrust, depression, shame, school conduct, social behavior, and sexuality. They also include the dysregulated qualities associated with ADHD: inattention and impulsivity. Several studies suggest that early childhood trauma may also interfere with the normal development and processing of neurotransmitters, including the one that keeps popping up in this discussion: dopamine. While genetic ADHD and traumatic ADHD often look the same, it is not yet clear whether they are.

Beyond Science
Over the past 40 years, there have been nearly 2,000 studies linking ADHD to multiple neurotransmitters, brain regions, genes, and environmental factors. Often the studies do not support each other. Some appear to be in direct contradiction. And, taken together, they still have not resolved the question that drives them all: what, exactly, is ADHD? In fact, there is a rising tide of opinion contending that ADHD is not a single disorder but several with similar symptoms. A 2017 brain imaging study conducted by Yale University’s Michael Stevens and his colleagues strongly suggested that executive function deficiencies and the three different subtypes of ADHD each originate in distinct and different parts of the brain. Although further studies are required to confirm this hypothesis, Dr. Stevens offered this opinion: “The most important thing at this point is to increase the awareness that not every patient who meets diagnostic criteria for ADHD has symptoms that arise from the same neurobiological abnormality.” At the very least, the wide variations in children’s ADHD symptoms and dysregulatory difficulties suggest that the condition may be multi-faceted and complex.

One source of the uncertainty has to do with limitations inherent in the research itself, obstacles in the time, technology, and funding that have been available to support it. Fortunately, in just the past few years, several new brain mapping projects have been launched worldwide, including the two largest – the European Union’s $1.3 billion HBP (Human Brain Project) and the U.S.’s $1 billion BRAIN (Brain Research Advancing Innovative Neurotechnologies) Initiative. In 2015 these mega-programs announced an international collaboration aimed at developing new techniques for brain study and a unified computational model that will describe all of the brain’s neural networks. Already the brain map is growing more detailed and the data more robust.

The work completed so far represents only a small fraction of the whole task. The endeavor is very young, immensely complicated, and still predicated on tools that, although sophisticated by current standards, will someday be regarded as primitive. No wonder the results are ambiguous. At this point they could hardly be otherwise. Hopefully, as researchers move forward, they will produce a vastly greater degree of clarity about brains in general and the ADHD brain in particular.

Or maybe not. Maybe there are much more fundamental obstacles to a true understanding of ADHD or any other “mental disorder.” In fact, these may be obstacles to a true understanding of the brain itself. The neurotypical brain is made up of approximately 100 billion neurons, each of which can have as many as 10,000 connections with other neurons. This means that the total number of possible connections in a healthy brain is something on the order of 10 to the 100th power. For context, consider that scientists estimate the total number of atoms in all the galaxies produced by the “big bang” to be between 10 to the 78th and 10 to the 82nd power. These same scientists generally agree that the human brain is the most complex system in the observable universe. It is currently beyond human comprehension and there is the possibility that it may always be so. The limits of our abilities to observe, to understand, and to interpret may never prove adequate to the full task of decoding the brain. Neither may the brain’s own power to construct what we regard as reality from the billions of light photons, sound waves, atomic particles, and chemical interactions that are encountered by our five senses and experienced by our bodies during every waking moment of every day. Moreover, the amount of information actually accessible by our senses is only a fraction of what actually exists and, of that, our brains only select and process the types of data required by us to function in our lives.

There may be yet another and more profound complication. Because the thing being studied, the brain, is also the thing doing the studying, the whole endeavor may be doomed from the start. Scientists and philosophers have long argued that a human brain cannot simultaneously be itself and see itself. If so, then it cannot truly hope to know itself, nor can it even hope to know what knowledge it lacks. Business people often talk about looking at phenomena “from outside the box.” With the brain, there may not be such thing as an “outside.” If all this is so, then the task of fully and clearly understanding the brain is inherently and inevitably impossible to accomplish. Behind every discovery is another mystery, and where the human brain is concerned it may always be so.