- Detecting dopamine dysfunction with pharmacological MRI
- Award date
- 22 November 2016
- Number of pages
- Vianen: Uitgeverij BOXPress
- Document type
- PhD thesis
- Faculty of Medicine (AMC-UvA)
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.
- Title on cover and spine: Detecting dopamine with pharmacological MRI.
The sections 'Acknowledgements | Dankwoord' and 'Curriculum Vitae' (pp. 198-203) have been placed under a permanent embargo and are not included in this online version of the thesis.
Thesis (Embargo until 22 November 2018)
Chapter 3: Repeated dexamphetamine treatment alters the dopaminergic system and increases the phMRI response to methylphenidate (Embargo until 22 November 2018)
Chapter 7: Age-dependent effects of methylphenidate on the human dopaminergic system in young vs adult patients with attention-deficit/hyperactivity disorder (Embargo until 22 November 2018)
Chapter 8: The age-dependent effects of a single-dose methylphenidate challenge on cerebral perfusion in patients with attention-deficit/hyperactivity disorder (Embargo until 22 November 2018)
Chapter 9: Long-term effects of stimulant exposure on cerebral blood flow response to methylphenidate in attention-deficit/hyperactivity disorder patients: does age-of-onset matter? (Embargo until 22 November 2018)
Chapter 10: Age-dependent effects of acute MPH on amygdala reactivity in stimulant treatment-naive patients with ADHD (Embargo until 22 November 2018)
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