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Amino acid challenge and depletion techniques in human functional neuroimaging studies: an overview

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Abstract

Imbalances of neurotransmitter systems, particularly serotonin (5-HT) and dopamine (DA), are known to play an essential role in many neuropsychiatric disorders. The transient manipulation of such systems through the alteration of their amino acid precursors is a well-known research tool. Among these methods are alterations of tryptophan, the essential amino acid (AA) precursor of 5-HT, as well as manipulations of tyrosine and phenylalanine, the AA precursors of DA, which can be metabolized into norepinephrine and subsequently into epinephrine. These systems can be loaded by applying a large dose of these AAs or depleted by applying an amino acid mixture lacking the respective AAs serving as precursors. Functional neuroimaging has given insights into differential brain activation patterns and functions depending on the tasks performed, pharmacological treatments or specific disorders. Such research has shed light on the function of many brain areas as well as their interactions. The combination of AA challenge approaches with neuroimaging techniques has been subject of numerous studies. Overall, the studies conducted in this particular field of research have shown that AA challenge techniques are valid and effective research tools that allow the investigation of serotonergic and dopaminergic systems without causing serious side effects or long-term damage to the subjects. In this review, we will present an overview of the results obtained so far and discuss the implications of these findings as well as open questions that remain to be answered.

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Acknowledgments

The research leading to these results is funded by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 602407.

Conflict of interest

FDZ was the recipient of an unrestricted award donated by the American Psychiatric Association (APA), the American Psychiatric Institute for Research and Education (APIRE) and AstraZeneca (Young Minds in Psychiatry Award). He has also received research support from the European Union (present work), the German Federal Ministry for Economics and Technology, the German Society for Social Pediatrics and Adolescent Medicine, from the Paul and Ursula Klein Foundation, the Dr. August Scheidel Foundation and a travel stipend donated by the GlaxoSmithKline Foundation. He is the recipient of an unrestricted educational grant donated by Shire Pharmaceuticals, Germany. He also received support from the Raine Medical Research Foundation (Visiting Professorship), and receives editor’s fees from Co-Action Publishing (Sweden). The other authors have nothing to declare and nothing to disclose.

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  1. Clinic for Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, RWTH Aachen University Hospital, Aachen, Germany

    C. S. Biskup, T. Gaber, K. Helmbold, S. Bubenzer-Busch & F. D. Zepf

  2. JARA Translational Brain Medicine, Aachen, Jülich, Germany

    C. S. Biskup, T. Gaber, K. Helmbold, S. Bubenzer-Busch & F. D. Zepf

  3. Department of Child and Adolescent Psychiatry, Faculty of Medicine, School of Paediatrics and Child Health and School of Psychiatry and Clinical Neurosciences, Dentistry and Health Sciences, The University of Western Australia (M561), 35 Stirling Highway, Crawley, Perth, WA, 6009, Australia

    F. D. Zepf

  4. Department of Health in Western Australia, Specialised Child and Adolescent Mental Health Services (CAMHS), Perth, WA, Australia

    F. D. Zepf

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  1. C. S. Biskup
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Biskup, C.S., Gaber, T., Helmbold, K. et al. Amino acid challenge and depletion techniques in human functional neuroimaging studies: an overview. Amino Acids 47, 651–683 (2015). https://doi.org/10.1007/s00726-015-1919-z

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