ADHD is not simply due to a shortage in dopamine
Attention Deficit Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by poor impulse control and an impaired regulation of attention. A common thought is that ADHD is caused by a shortage of dopamine, one of the major neurotransmitters in the brain. We recently conducted a survey to test people’s knowledge of ADHD (unpublished work). The majority of the 225 participants either was not sure whether ADHD is caused by a shortage in dopamine (59%) or believed this was true (13%). In this blog post, I will explain why this is a misconception and explain the actual role of dopamine in ADHD.
The misconception likely stems from limitations of studies in the early days of neuroimaging research (see Arnsten & Pliszka, 2011). At this time, Positron Emission Tomography (PET) studies allowed researchers to visualize the presence of dopamine in the midbrain, but no other neurotransmitters or brain areas. This research pointed to reduced levels of dopamine in the midbrain of individuals with ADHD. Further, early work in rat models of ADHD demonstrated that high doses of stimulant ADHD medication resulted in pronounced increases of dopamine release in the entire brain.
“This was interpreted as evidence for a shortage of dopamine in ADHD, and became known as the ‘hypodopaminergic state hypothesis’ of ADHD.”
A disorder that is unequivocally caused by a shortage of dopamine is Parkinson’s Disease (PD). PD is due to a progressive loss of dopamine-producing cells in the midbrain, which results in motor symptoms such as slowness of movement, tremor, and rigidity, as well as cognitive impairments, including deficits in executive functioning, attention, memory, and visuospatial functioning (Koerts et al., 2009; 2012). These motor symptoms and cognitive impairments become worse over time. Importantly, ADHD has a very different clinical presentation.
“This already insinuates that the hypodopaminergic state hypothesis cannot be true.”
Another interesting way to formally test the hypodopaminergic state hypothesis of ADHD is by examining the frequency of spontaneous eye blinks. Early work in non-human primates demonstrated that dopamine-stimulating medications produce increases in blink rate whereas dopamine-inhibiting medications produce decreases in blink rate (see Groen et al., 2015). Further, patients with PD have two times lower blink rates than healthy individuals (Deuschl & Goddemeier, 1998). Sometimes they even suffer from medical eye problems because their eyes are no longer sufficiently protected from dehydration and filth.Spontaneous blink rate can thus be regarded as a reliable marker of the integrity of the dopamine system in the brain. We recently examined spontaneous eye blink rates in children with ADHD (Groen et al., 2015) and in contrast to the hypodopaminergic state hypothesis we found no reductions; neither did previous studies. Therefore, if it exists, the hypodopaminergic state in ADHD thus is much less pronounced than in for example PD.
The current ‘revisited’ dopamine hypothesis of ADHD holds that the transmission of dopamine between neurons as especially reduced in the prefrontal brain (see Arnsten & Pliszka, 2011; Levy & Swanson, 2001). This brain area is responsible for the regulation of actions, attention, and emotions, and ultimately for goal-directed behavior. Metaphorically speaking, one could compare the prefrontal brain to the conductor of an orchestra, who regulates the musicians who are responsible for actions, attention, and emotions. The reduction in neural transmission is due to malfunctioning dopamine transporters and receptors in this area, which has been demonstrated by research using more refined PET techniques as well as genetic and pharmacological approaches.
“So it is not a lack of dopamine causing ADHD, but rather a reduced neural transmission of dopamine in the prefrontal brain.”
However, this is only half of the story because there is another major neurotransmitter that, in concert with dopamine, is responsible for optimal functioning of the prefrontal brain: noradrenaline (Arnsten & Pliszka, 2011).
“Due to reduced neural transmission of both dopamine and noradrenaline, the prefrontal brain of individuals with ADHD is generally ‘under stimulated’ or ‘under aroused’.”
This might sound counterintuitive as individuals with ADHD often appear over active, but ‘under arousal’ of the prefrontal brain leads to unguided actions, attention, and emotions. Metaphorically speaking, the conductor of the orchestra is ‘lazy’, so that actions, attention or emotions can easily take the lead and get out of control. This ‘under stimulation’ explains why taking low doses of ‘stimulant’ ADHD medication (such as methylphenidate) improve symptoms of ADHD. This type of medication optimizes the prefrontal neural transmission in individuals with ADHD by targeting the dopamine and noradrenaline transporters. The brain mechanisms of ADHD are therefore much more complex than simply a shortage in dopamine.
Arnsten, A.F.T., & Pliszka, S.R. (2011). Catecholamine influences on prefrontal cortical function: Relevance to treatment of attention deficit/hyperactivity disorder and related disorders. Pharmacology Biochemistry and Behavior, 99, 211-216.
Deuschl, G., & Goddemeier, C. (1998). Spontaneous and reflex activity of facial muscles in dystonia, Parkinson’s disease, and in normal subjects. Journal of Neurology, Neurosurgery and Psychiatry, 64, 320-324.
Groen, Y., Börger, N.A., Koerts, J., Thome J., & Tucha O. (online first 2015). Blink rate and blink timing in children with ADHD and the influence of stimulant medication. Journal of Neural Transmission, DOI 10.1007/s00702-015-1457-6.
Koerts, J., Leenders, K.L. & Brouwer, W.H. (2009). Cognitive dysfunction in Parkinson’s disease: Automatic and controlled behavior. Cortex, 45, 922-929.
Koerts, J., Van Beilen, M., Leenders, K.L., Brouwer, W.H., Tucha, L. & Tucha, O. (2012). Complaints about impairments in executive functions in Parkinson’s disease: The association with neuropsychological assessment. Parkinsonism and Related Disorders, 18, 194-197.
Levy, F. & Swanson, J.M. (2001). Timing, space and ADHD: The dopamine theory revisited. Australian and New Zealand Journal of Psychiatry, 35, 504-511.