The acronym ADHD stands for attention-deficit hyperactivity disorder, a complex clinical entity that affects mostly children and adolescents, and whose main symptoms include abnormal levels of hyperactivity, impulsivity and/or inattention.
Currently, although ADHD is considered to be a brain disorder, the exact neurobiological mechanisms underlying this condition are unknown, nor has an effective genetic marker been discovered that can be used to make a reliable diagnosis, apart from psychological tests and cognitive and behavioural assessments.
In this article we review the current state of research on the neurobiology of ADHD , the main genetic and brain imaging studies that have been conducted, and the theories that try to explain how and why this disorder develops.
What is known about ADHD?
Attention Deficit Hyperactivity Disorder (ADHD) is a clinical picture diagnosed on the basis of persistent levels of hyperactivity, inattention and impulsivity . Currently, there are no biomedical tests capable of detecting ADHD and the diagnosis is based on the observation of certain behavioural symptoms.
The lack of a physical cause or several causes that prove the existence of this disorder has generated some controversy in the scientific community and in society in general, and treatments based on psychostimulant medication for children and adolescents have been questioned. However, the effectiveness that pharmacological treatment has in many cases has led researchers to suspect that there is an underlying neurobiological etiology.
Current research on ADHD from a neurobiological point of view focuses, above all, on the theoretical framework that involves studying the alteration of dopaminergic activity (its receptors and transporters), as well as its implications in the generation of the symptomatology of this disorder.
Today, the neuroscientific community continues to deal with the concept of inhibitory response control deficit, which is the inability of people with ADHD to control and inhibit impulses and cognitive responses, which ends up interfering with the executive functions that plan, coordinate and execute the final behaviors.
Current research on ADHD is therefore focused on finding the neurobiological mechanisms that explain the disorder and on genetic markers that serve as a reliable diagnostic basis. Let’s see below what are the main theories on the neurobiology of ADHD.
Neurobiology of ADHD
There is an extensive scientific literature on the neurobiology of ADHD focusing on motivational processes and cognitive control in children with this disorder . For example, behavioural reinforcement has been widely researched and in recent years there have been great advances in understanding the neuronal mechanisms involved in the processing of reinforcements.
It has been suggested that dopamine plays an important role as a mediator in signaling cognitive reinforcement. The structures that have emerged to play a central role in the mechanisms of learning reinforcement are those innervated by
dopaminergic projections of the midbrain. In fact, some of these same structures have been implicated in ADHD, since in this disorder there is an alteration in the processing of rewards.
The dopaminergic theory is based on the existence of deficits in two regions in which dopamine plays a crucial role : the anterior cingulate, whose hypoactivation produces a cognitive deficit; and the caudate nucleus, whose overactivation generates an excess of motor behaviors, typical in subjects with ADHD.
Although there appears to be considerable evidence in favour of the dopaminergic theory, research has also focused on the role of other possible candidate genes, such as the norepinephrine transporter NET1, or the dopamine receptor gene DRD1. However, no biological marker for ADHD has been detected so far and its diagnosis continues to be based on observational method and neurocognitive assessments.
Research with family members has consistently indicated a strong genetic contribution to ADHD. Studies with twins have shown a high heritability of this disorder . It is likely that multiple genes with a moderate effect are involved, as to date no single gene has been found to play a major role.
Researchers have focused on studying genetic variations in the dopamine D4 receptor and the dopamine DAT1 transporter, but they have found that individually they have only weak effects and none are necessary or sufficient for ADHD to occur. In fact, a recent review of several molecular genetics studies concluded that there were significant associations for four genes in ADHD: the dopamine D4 and D5 receptors, and the dopamine and serotonin transporters.
However, there is a growing recognition among the scientific community that there is a potential interaction between genetics and environmental risk factors . Without diminishing the importance of genetic factors, environmental factors that increase the risk of ADHD have also been identified, such as exposure to lead or polychlorinated biphenyls during early childhood, although their effects are not specific to ADHD.
Brain imaging studies
Serious anatomical changes in brain dimensions associated with ADHD have been observed in brain imaging studies. The most consistent finding is a reduction in total brain size that persists into adolescence , and the reduction in size of several brain regions, such as the caudate nucleus, prefrontal cortex, white matter and corpus callosum, and the cerebellar vermis.
A meta-analysis conducted in 2007 concluded that the caudate nucleus and globus pallidus, which contain a high density of dopamine receptors, were smaller in subjects with ADHD than in the control groups. In addition, a decrease in the blood supply in regions of the striatum was also observed, as well as changes in the binding of the dopamine transporter.
Studies of cortical thickness have also shown changes in ADHD. A regional reduction in the thickness of the cerebral cortex has been detected, associated with the DRD4 allele , which is widely related to the diagnosis of ADHD. This cortical thinning is more evident in childhood and, to a large extent, seems to resolve during adolescence.
Tractography images have also detected alterations in the frontal white matter and cerebellum of children and adolescents with ADHD. On the other hand, in reinforcement and reward tasks, in subjects with ADHD a preference for the immediate over delayed reinforcement is observed. And in studies with functional magnetic resonance in adolescents with ADHD it has been shown that there is a reduction of the ventral striatum when reward is anticipated, contrary to what happens with control subjects in whom this brain region is activated.
Curatolo, P., D’Agati, E., & Moavero, R. (2010). The neurobiological basis of ADHD. Italian journal of pediatrics, 36(1), 79.
Kollins, S. (2009). Genetics, neurobiology, and neuropharmacology of attention deficit hyperactivity disorder (ADHD). Revista Española de Toxicomanías, 55, 19-28.
Yunta, J. A. M., Palau, M., Salvadó, B., & Valls, A. (2006). Neurobiology of ADHD. Acta Neurol Colomb, 22(2), 184-189.