Attention-deficit/hyperactivity disorder (ADHD) is among the most common neurological disorders diagnosed in children and adolescents. The American Psychiatric Association states that according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5, 2013), 5% of children have ADHD. However, other studies conducted in smaller community samples report higher rates (American Psychiatric Association, 2013). ADHD can be classified into a number of subcategories including but not limited to neurodevelopmental and neurobehavioral disorders. It is characterized by inattention, hyperactivity, and impulsivity and can have an impact on one’s emotions, behaviors, and ability to learn new things (Gehricke et al., 2017).
Epidemiological studies conducted over the past decade have documented high rates of concurrent psychiatric and learning disorders among individuals with ADHD (Wilens & Spencer, 2010). This may include disruptive, mood, anxiety, and substance abuse disorders, some of which can share symptoms with ADHD. There is not one simple test that can diagnose ADHD in children or adults, so it’s important to distinguish between other disorders and rule out other conditions. The DSM-5 includes a detailed diagnostic evaluation of behavior to help psychiatrists, neurologists, and family physicians in diagnosing this disorder. Children typically display symptoms before the age of 7 (Roth & Rosen, 2017).
ADHD has been found to affect various brain structures. This remains an area of interest to many researchers who aim to attribute symptoms and deficits in executive functioning to neurobiology. Structural imaging studies are one of the most revealing methods to demonstrate the biological and anatomical abnormalities found in children and adults with ADHD. A large study by Castellanos and colleagues reported a smaller total cerebrum, cerebellum, and four cerebral lobes, while another study of adults with and without ADHD revealed a smaller anterior cingulate (ACC) and dorsolateral prefrontal cortex (DLPFC) (Wilens & Spencer, 2010). The DLPFC controls working memory which involves the ability to retain information while processing new information. The ACC is a key region of regulation involving the ability to focus on one task and choose between options. Therefore, these differences are thought to account for deficits in goal-directed and on task behaviors in those with ADHD.
In a study conducted by Gehricke et al. (2017), structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) revealed ADHD in young adults was associated with decreased grey matter concentration, increased white matter concentration, and decreased shape in widespread areas including frontal, temporal, striatal, partial, and limbic regions. Specifically, there were reduced grey matter concentrations found in regions of the right frontal gyrus, right temporal gyrus, left caudate head, and left parahippocampal gyrus. There were also widespread changes to the maturation of white matter fiber bundles in the brain indicating incomplete maturation. These findings may also suggest that the cortico-limbic associated circuitry is dysfunctional in people with ADHD (Gehricke et al., 2017). This connects the amygdala with the thalamus and the orbitofrontal cortex, and is primarily responsible for emotional learning and behavioral regulation. This may explain some of the disruptive behaviors such as dysfunctional motivation, impulsivity, and emotionality that are often associated with ADHD.
Gehricke et al.’s results were in agreement with previous findings on cerebral and cerebellar volumetric reductions associated with ADHD, such as Castellanos and colleagues’ work. An abundance of research exists demonstrating potential abnormalities associated with other various brain structures in individuals with ADHD. However, a meta-analysis of structural imaging findings revealed that the most consistent finding is the overall reduction in total brain size and reduced dimensions and cortical thickness of several brain regions including the caudate nucleus, prefrontal cortex white matter, corpus callosum and the cerebellar vermis (Tripp & Wickens, 2009). Many of the structural changes associated with an ADHD diagnosis in childhood continue to be affected in young adulthood (Gehricke et al., 2017).
The pathophysiology of ADHD consists of not only structural differences, but also relates to neurotransmitters which can further explain disruptions of circuitry discussed. According to Silver, ADHD was the first disorder found to be the result of a deficiency of a specific neurotransmitter, in this case, norepinephrine. Impaired neurotransmitter activity is seen in four functional regions of the brain. The frontal cortex is responsible for higher-level functioning, so a deficiency here may cause inattention, problems with organization, or impaired executive functioning. A deficiency in the region of the limbic system, located deeper in the brain, may result in restlessness or emotional volatility. The neural circuits found throughout the basal ganglia regulate communication within the brain, so a deficiency here may cause information to “short-circuit,” resulting in inattention or impulsivity. Lastly, Silver concludes that a norepinephrine deficiency in the reticular activating system, which is the major relay system among many pathways in and out of the brain, can also cause inattention, impulsivity, or hyperactivity (Silver, 2018).
Changes in dopamine transporter binding have also been described in the human striatum in ADHD. Extensive knowledge regarding the neural circuits that underlie reinforcement can be applied to understanding how children with ADHD process reward differently than those without ADHD. Tripp and Wickens state that dopamine has been strongly implicated a mediator of the brain’s reinforcement signal. Dopaminergic projections from the midbrain innervate structures that are known to play a role in reinforcement learning mechanisms. Therefore, alterations in dopamine function may explain some of the symptoms of ADHD (Tripp & Wickens, 2009).
Family, twin, adoption, and segregation analysis studies have revealed that ADHD is strongly influenced by genetic factors (Furman, 2008). Research conducted by Rietveld and associates showed a mean heritability rate of 75% (Rietveld et al., 2004). While some researchers have had success in identifying specific candidate genes that contribute to ADHD, pooled analyses revealed that there is not one single gene associated with the disorder. Wilens and Spencer (2010) state that, “As with many complex neuropsychiatric conditions, multifactorial causation is thought to be involved in ADHD; an additive effect of multiple vulnerability genes interacting with environmental influences.” The combination of these small effects result in the classification of ADHD as a polygenic disorder. Some of the previously discovered genes include the post-synaptic DRD3, dopamine transporter, and SNAP 26 genes, most of which relate to synthesis, packaging, release, detection, and recycling of dopamine, catecholamines, or serotonin (Wilens & Spencer, 2010). Polymorphisms of the D4 and D5 receptors, as well as variations of the DAT1 gene have also been associated with ADHD (Tripp & Wickens, 2009). It is important to note that non-inherited environmental factors also contribute to ADHD (Thapar et al., 2012).
ADHD encompasses a wide range of symptoms and differs amongst individuals dependent on a number of other contributing factors. It remains difficult to properly identify and diagnose this disorder, which is a dilemma that will likely persist until science can advance even further. The neuroscience involving associated brain structures, connectivity, mechanisms, and genetics of ADHD has proven to be significant in helping to better understand it, but a great amount of information still remains unclear. Although medication was not discussed in this review, there are various forms that have demonstrated promising effects in many children and adults. In addition to pharmacological interventions, psychosocial interventions may be effective in producing an overall positive outcome for those diagnosed with ADHD.