ADHD is a highly heritable condition. There are very few medical disorders or traits as genetic as this one. For example, studies reveal that the ADHD syndrome is almost as heritable as your height. But how do we know this?

Close relatives (immediate family) of an ADHD child have been found to have an approximately five times increased risk of having it themselves. But of course this clustering of ADHD within families could be due to shared factors in the home environment, so what was needed was a way of controlling for these environmental factors. Twin studies provide the means to do this. Identical twins share 100% of their genes, and non-identical twins fifty percent. If the identical twin-pairs show more similarity in their symptoms than the non-identical twins, it follows that there is a genetic component at play. And many twin studies have in fact shown this to be the case. Adoption studies have provided us with further evidence. If the environment was the only causative factor, one would expect adopted children (especially those adopted at birth) to be more like their adoptive families. But numerous studies show that adopted children are more similar to their biological relatives, on various measures of ADHD, than to their adoptive relatives.


Which genes are to blame?

A gene is the basic unit of heredity and is the vehicle for transmission from one generation to the next. Each gene comprises a sequence of DNA (a highly specialised chemical sequence) which codes for a particular protein, which in turn has some functional role within the cell and organism. We all have many genes (about 30,000) inherited from our parents, coding for the numerous characteristics or traits which make us unique individuals. In every cell, there are two copies of each gene, one from the father and one from the mother.

For our purposes, we will focus on those genes which play a role in brain functioning, and more specifically, in areas of the brain which are known to be affected in ADHD, the prefrontal area (at the front of the brain, beneath your forehead) and the cerebellum (at the back of the brain). These areas of the brain have been implicated in ADHD by means of sophisticated imaging studies. Now, let’s imagine we’re looking at a piece of brain under the microscope. What you would see is lots of individual cells – in the brain we call them neurons – each surrounded by a cell membrane, as are cells anywhere in the body. Neurons are arranged in such a way as to communicate with each other across tiny gaps called synapses. The synapse occurs where the cell membrane of one neuron (let’s call it neuron A) is in very close proximity to that of another (neuron B). Numerous such communicating neurons contribute to pathways or circuits, which allow for different areas of the brain to ‘talk’ to each other. This communication between neurones is facilitated by chemical messengers (called neurotransmitters) in the brain, of which dopamine is probably the most important in ADHD. It was thus logical, in searching for culprit ADHD genes, to begin with those involved in dopamine functioning, and … Voila! Enter the dopamine receptor gene, the gene which codes for the dopamine receptor protein, DRD4.

Here is where DRD4 fits in. After having been produced in neuron A, dopamine exits the cell membrane, works its way across the synapse and communicates with neuron B. It does so by attaching itself to the dopamine receptor protein (DRD4) on the cell membrane of neuron B. Dopamine ‘docks’ on this receptor, which in turn triggers a series of events in neuron B, allowing the communication to continue along the circuit. In this manner, the message is transmitted from one area of the brain, along a pathway, to another area.

As with any gene, we all have two DRD4 copies, one from each parent. These parental copies of genes are referred to as ‘alleles’ (pronounced al-eel). Thus for each gene, you will have two alleles. These alleles often differ, emanating as they do from two different people, and hence two different gene pools. One of the variants of the DRD4 gene is known as the 7-repeat allelic variant, so named because of a specific pattern observed in the DNA sequence. We will call it 7R for short. If you take a group of kids with ADHD and compare them with a group of unaffected children, significantly more of those with the condition will have this offending, 7R allelic variant of the DRD4 gene. Generally, children and adults with this genetic variant tend to be more novelty-seeking, impulsive, restless and inattentive than those without it. Other genes have also been implicated in the condition, and because there are several genes involved, ADHD is referred to as a polygenic disorder. This is in contrast to certain other conditions, such as cystic fibrosis, for example, which is caused by one specific genetic variant.


But it’s not all about genes

Overall, twin and adoption studies reveal a genetic contribution of 70-80% to the observed symptoms of ADHD, which means that a significant chunk must be non-genetic, due to environmental factors. Several such environmental factors have been identified, and they all seem to operate really early on in life. As early as the womb. A mother’s smoking or drinking in pregnancy, for example, is a strong independent risk factor for her offspring having ADHD, even when you control for genes and other environmental factors. Other risks in pregnancy include alcohol consumption and maternal stress. Prematurity and birth complications, resulting in insufficient blood flow and oxygen to the brain, are additional risk factors for ADHD, even when there is no obvious brain damage in the aftermath of the delivery. Other medical causes include epilepsy, brain infections including encephalitis, HIV/AIDS and various congenital and genetic conditions.

The plastic brain and attachment

In the first two years of a child’s life, vital neurobiological changes are occurring. The infant’s brain is highly ‘plastic,’ which means that it is changing and remodelling constantly. It is also growing at a fast rate; by the age of two, the brain is already 80% of its adult size. This is also the period when neuronal pathways receive a thick outer covering called myelin, which allows for faster and more efficient transmission of impulses. By the age of fifteen months, the density of synapses in certain areas of the brain reaches its peak, after which growth slows down. Thereafter, there is more refinement, reorganisation and ‘pruning,’ a process by which – as in the garden – inefficient neurons and synapses are culled. Meanwhile, in parallel with these biological brain events, the crucial process of attachment is unfolding.

Attachment refers to the close emotional bonds of affection which develop between babies and their primary caregivers. A newborn baby can be handed to anyone with no distress, but over the next few months the baby begins to show a preference for, and seeks out, a specific person. This is the beginning of attachment. Children will form attachments to various people over time, but the first and most important attachment relationship is almost always with the mother. There are critical periods – a timetable, if you like – during which aspects of attachment should be occurring. By about 18 months, the attachment experience is then ‘wired in,’ and the consequences are far-reaching. Depending on what happens between the mother and child in these crucial early months, children may become either securely or insecurely attached. If the mother is erratic, unpredictable, or unavailable, healthy attachment cannot occur. This is why it is so important to recognise and treat postnatal depression, a condition in which the mother cannot provide the emotional availability which her child requires.

To become securely attached, an infant requires a primary caregiver who is consistently present, and attuned enough to the child to respond appropriately to her need for focused attention, physical affection and stimulation. Healthy attachment leaves the child with an ‘internal working model,’ or template, which allows her to see herself as valued, and others as ‘basically good.’ This facilitates healthy relationships in childhood and later life. In addition, studies have shown that securely attached children have longer attention spans and show more persistence in tasks. Interesting findings, considering that children with ADHD show impairments in these very areas…

Another vitally important aspect of the child’s psychological environment is the emotional milieu of the home. Maternal hostility, high levels of criticism and a lack of maternal warmth, whilst not causative factors per se, all affect the prognosis in ADHD, mediating the progression to more serious behavioural disturbances such as conduct disorder. The converse is also true; maternal warmth in particular, seems to predict a better outcome in kids with ADHD.


Finding middle ground

OrchidThus the available evidence suggests that both nature and nurture are important. For the past fifteen years or so, the prevailing theory linking these competing theories has been the so-called ‘stress-diathesis model.’ You may have inherited the bad gene, say the 7R allele of DRD4, but only only with the additive, compounding effect of stressful circumstances will the condition manifest. This implies an interaction between the environment and your genes. A relatively new theory of genetics, called the orchid  hypothesis further expounds on this gene-environment interaction. The concept of ‘dandelion children’ has been around for a while, describing kids who are resilient and will cope in most circumstances; they will be okay even with average care. In contrast, ‘orchid children,’ who possess the risk alleles such as DRD4, are particularly sensitive to their rearing conditions. Given the right environment, they bloom spectacularly, but if neglected they quickly wither and wilt. Whether good or bad, the environment has a pronounced effect on how they turn out.

And there is good evidence to back this up. Compared to children without the DRD4 7R allele, the behaviour of those with this variant has been found to be more sesnsitive to the quality of parenting received, and to have a better treatment response to parenting interventions. Thus these risk alleles confer a sensitivity, not only to negative experience, as the stress-diathesis model would have it, but to all experience. They open the window wider, not just to the adverse environment, but to the whole environment, good or bad. This is both scary and exciting. The stakes are high, and getting the environment right just became a whole lot more important, at least for a certain group of kids.

Genetic volume control

Until now, we have all thought in a somewhat fatalistic and deterministic manner about our genetic makeup; that it’s the hand we’ve been dealt and we just need to suck it up and move on. Not so, it seems. In recent years, geneticists have discovered an increasing number of environmental influences – both physical and psychological – which can actually change gene activity, effectively switching genes on or off, telling them to shout loudly or to whisper. Furthermore, these changes – known as epigenetic changes – can be transmitted from one generation to the next. What this means is that the choices we make can influence the expression of our genes for better or worse, having an influence on the generations to come. I hope you are as excited about that as I am.

It works something like this. You inherit a particular gene from one of your parents, let’s say the 7R DRD4 variant. It turns out that the expression of that gene is not a given. Rather, there are several environmental factors which might determine how influential it becomes. For example, if mom is extremely stressed in the pregnancy, her stress hormones, including cortisol, cross the placenta, enter your bloodstream and then your developing brain. These unusually high levels of cortisol cause your 7R gene to get methylated, thus activating it, and manifesting down the line with the clinical condition of ADHD. Your younger brother inherits the exact same allele, but by then the financial problems and dad’s alcohol abuse have been sorted out, and a tranquil pregnancy ensures that his 7R variant remains quietly in the background.

So the next time you discuss this at a dinner party you are entitled to say that the ‘nature versus nurture’ debate is actually so last century. The answer lies in a complex set of interactions between genes and the environment. But the really exciting news is that the genetic influence, although strong, is not immutable and is readily affected by decisions that you and I make about our parenting.

And I like that.