Pharmacological MRI in the assessment of monoaminergic function

The results of this thesis demonstrate that phMRI is a valuable added tool in the imaging of monoaminergic function. I have shown that the i.v. administration of dAMPH leads to a significant hemodynamic response in DAergic areas, most likely reflecting attenuation of DAergic signalling. In addition, resting state studies demonstrated alterations in functional connectivity networks involved in DAergic signalling. Moreover, altered DAergic responses were also demonstrated using fMRI involving a DAergic task.
A second series of experiments showed that MPH, although giving a different response than i.v. dAMPH, also influences the hemodynamic response in monoaminergically relevant areas. Also with BOLD based fMRI, MPH was shown to greatly affect DAergic function studied using fMRI shows that MPH has a great influence on signalling in adult humans. The assessment of alterations of monoaminergic functions caused by psychotropic drugs has been sufficiently demonstrated in adult populations by comparing healthy adults to dAMPH users. The chronic use of dAMPH demonstrably alters responses to an oral MPH challenge.
Finally, we showed that chronic use of MDMA leads to a difference in the hemodynamic response to a challenge with the SSRI citalopram, which overlapped with the SPECT findings. These experiments taken together implicate that these techniques can be applied in research performed in children in order to safely assess neurodevelopment of monoaminergic systems and variations in this development either physiological or induced by external interventions. In addition, it provides further evidence that dAMPH use alters DAergic function and may indeed lead to neurotoxic alterations of the DAergic system.