Attention Deficit Hyperactivity Disorder - Pathophysiology

Pathophysiology

The pathophysiology of ADHD is unclear and there are a number of competing theories. Research on children with ADHD has shown a general reduction of brain volume, but with a proportionally greater reduction in the volume of the left-sided prefrontal cortex. These findings suggest that the core ADHD features of inattention, hyperactivity, and impulsivity may reflect frontal lobe dysfunction, but other brain regions in particular the cerebellum have also been implicated. Neuroimaging studies in ADHD have not always given consistent results and as of 2008 are used only for research and not diagnostic purposes. A 2005 review of published studies involving neuroimaging, neuropsychological genetics, and neurochemistry found converging lines of evidence to suggest that four connected frontostriatal regions play a role in the pathophysiology of ADHD: The lateral prefrontal cortex, dorsal anterior cingulate cortex, caudate, and putamen.

In one study a delay in development of certain brain structures by an average of three years occurred in ADHD elementary school-aged patients. The delay was most prominent in the frontal cortex and temporal lobe, which are believed to be responsible for the ability to control and focus thinking. In contrast, the motor cortex in the ADHD patients was seen to mature faster than normal, suggesting that both slower development of behavioral control and advanced motor development might be required for the fidgetiness that characterizes ADHD. It should be noted that stimulant medication itself may affect growth factors of the central nervous system.

The same laboratory had previously found involvement of the "7-repeat" variant of the dopamine D4 receptor gene, which accounts for about 30 percent of the genetic risk for ADHD, in unusual thinness of the cortex of the right side of the brain; however, in contrast to other variants of the gene found in ADHD patients, the region normalized in thickness during the teen years in these children, coinciding with clinical improvement.

Previously it was thought that the elevated number of dopamine transporters seen in ADHD patients was part of the pathophysiology of ADHD but it now appears that the reason for elevated striatal dopamine transporter density in ADHD individuals is due to neuroadaptations occurring due to the continuous exposure to stimulants such as methylphenidate or dexamphetamine as the body tries to counter-act the effects of the stimulants by developing a tolerance to the stimulant medications. One interpretation of dopamine pathway tracers is that the biochemical "reward" mechanism works for those with ADHD only when the task performed is inherently motivating; low levels of dopamine raise the threshold at which someone can maintain focus on a task that is otherwise boring. There is evidence that people with ADHD have a low arousal threshold and compensate for this with increased stimuli, which in turn results in disruption of attentional capacity and an increase in hyperactive behaviour. The reason for this is due to abnormalities in how the dopamine system in central nervous system responds to stimuli.

Critics, such as Jonathan Leo and David Cohen, who reject the characterization of ADHD as a disorder, contend that the controls for stimulant medication usage were inadequate in some lobar volumetric studies, which makes it impossible to determine whether ADHD itself or psychotropic medication used to treat ADHD is responsible for the decreased thickness observed in certain brain regions. While the main study in question used age-matched controls, it did not provide information on height and weight of the subjects. These variables it has been argued could account for the regional brain size differences rather than ADHD itself. They believe many neuroimaging studies are oversimplified in both popular and scientific discourse and given undue weight despite deficiencies in experimental methodology.