Detecting dopamine dysfunction with pharmacological MRI

This thesis aims to further characterize the neurobiological origins underlying the pharmacological magnetic resonance imaging (phMRI) signal. phMRI is an MRI technique that measures the hemodynamic response to a psychotropic drug in order to non-invasively visualize neurochemical processes in the brain. Our second aim was to use this knowledge to investigate the effects of methylphenidate (MPH), used in the treatment of attention-deficit/hyperactivity disorder (ADHD), on the developing dopamine (DA) system (i.e. its age-dependency).
Our results from studies in amphetamine users and ADHD patients are promising as they show that phMRI can detect DA abnormalities in the human brain. However, further technological improvements are necessary to improve the sensitivity and specificity of the technique and to allow advancement of this field. In addition, we showed for the first time that ADHD medications, such as MPH, have differential effects on the developing compared to the matured brain in humans; in a randomized clinical trial the cerebral blood flow in response to MPH was increased in children, but not adults, treated with MPH for four months. This has important implications with regard to the use (and increased prescription rates) of MPH in the treatment of ADHD, because the brains of children are still developing. Therefore, our findings stress the need for future studies on the long-term effects of MPH in children.