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Uncovering dopamine deficits in schizophrenia through advanced imaging

Neuroimaging tools offer invaluable perspectives on the neurochemistry and function of the brain in schizophrenia. In the lead-up to the international CINP 2016 congress in Seoul, Korea,* we spoke with Professor Anissa Abi-Dargham, from New York in the USA, about how imaging is revealing unexpected aspects of dopaminergic dysfunction to be characteristic features of schizophrenia.

Professor Anissa Abi-Dargham MD is currently Professor of Psychiatry and Radiology at Columbia University Medical Center and Director of the Division of Translational Imaging at the New York State Psychiatric Institute, New York, USA. She is the lead investigator for the US National Institute of Mental Health (NIMH) study of "Dopamine Dysfunction in Schizophrenia”.  She will soon be Professor of Psychiatry at Stony Brook University (as of July 1st) and Vice Chair for Research in the Department of Psychiatry.


Can you describe how brain imaging techniques help our understanding of the neurochemistry of schizophrenia?


Imaging techniques allow us to examine anatomy and function of the brain in live subjects, which is a unique opportunity to understand how the findings in the brain relate to behaviour and function, as well as symptoms in patients.


What has positron emission tomography (PET) imaging revealed about circuitry and dopaminergic dysfunction in schizophrenia?


PET imaging allows us to look at receptors and neurotransmitters in a way that is not possible with magnetic resonance Imaging (MRI). We are able to access and study dopaminergic dysfunction in patients with schizophrenia and we have confirmed that the condition is associated with excessive striatal presynaptic dopamine leading to excess D2 receptor stimulation. This in turn is associated with psychosis. But what has been harder to do is to examine other parts of the brain – like the frontal cortex – areas involved in cognition, executive functions and working memory. The latest PET imaging techniques now show us that there are actually profound deficits in cortical dopamine and that indeed there are dopaminergic deficits in many other regions outside of the striatum.


Why is it important to understand mechanistic changes in the schizophrenic brain?


Imaging techniques allow us to investigate changes in the very early stages of the disease, and can be used to assess effects of treatments for schizophrenia. There have been imaging studies of the prodromal stage of schizophrenia. Imaging studies are helping to show that our current treatments – based on D2 blockade – may not be enough to address the dopaminergic changes in schizophrenia. Now that we know there are areas of the brain where there is too little dopamine release – we may need to rethink our treatment approaches, and work harder to find treatments to enhance and manage these dopaminergic deficiencies.


What are the main key points and learnings for delegates at CINP attending your plenary lecture on the 3rd of July?


I hope delegates will get an update on the topography of dopaminergic dysfunction in schizophrenia, the nature of the dopaminergic dysfunction, and how the different aspects of dopamine dysfunction correlate with the symptom domains of schizophrenia.

For example the striatal dopamine excesses appear to correlate with psychosis, while the cortical deficits seen on imaging appear to relate to abnormal activation during performance tasks and poor working memory capacity.

Delegates will also come to understand the dopaminergic changes in schizophrenia in the context of lots of other abnormalities and we will discuss whether the changes we see in schizophrenia are a downstream consequence or are more proximal to disease course.

We need to know more about the cellular and molecular events that bring schizophrenia about – and that will come with more study – looking at stem cells from patients with schizophrenia, studying extreme phenotypes, developing better animal models of schizophrenia, and tapping into the explosion in basic understanding of genes conferring risk for schizophrenia.

* Professor Abi-Dargham will give one the first plenary lectures on the opening day of the CINP in Seoul (PL01 3 July at 08:45): visit https://www.cinp2016.com

Our correspondent’s highlights from the symposium are meant as a fair representation of the scientific content presented. The views and opinions expressed on this page do not necessarily reflect those of Lundbeck.

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