Shitij Kapur & Oliver Howes on the Dopamine Hypothesis of Schizophrenia
Fast Breaking Commentary, October 2010
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Article: The Dopamine Hypothesis of Schizophrenia: Version III-025EF—The Final Common Pathway
Authors: Howes, OD;Kapur, S |
Shitij Kapur & Oliver Howes talk with ScienceWatch.com and answer a few questions about this month's Fast Breaking Paper paper in the field of Psychiatry/Psychology.
Why do you think your paper is highly
cited?
The role of dopamine in schizophrenia is one of the few documented and replicated realities in schizophrenia. It is very central to our understanding of schizophrenia—and what is particularly satisfying about it is that it relates not only to pathophysiology, but also to treatment and also to theories of psychopathology. So, it is a satisfying piece of work.
The reason the article may be highly cited is because it brings this information together and proposes a mechanism that links risk factors to these brain changes. Reviews about dopamine in schizophrenia are not by themselves unique or new. We think that if our paper has more resonance than others, it is because we were giving a decidedly newer take than was available in the most-cited review on this matter by Davis et al., published almost two decades ago.
Does it describe a new discovery, methodology, or
synthesis of knowledge?
It is a synthesis of new knowledge. In particular, it synthesizes new knowledge from genetics, imaging, sociobiological findings, and psychological theories.
Would you summarize the significance of your paper
in layman's terms?
Lead author
Oliver D. Howes.
Description: P.E.T Scan Positron Emission
Tomography (PET) machine.
For a long time we have known that patients with schizophrenia have some change in chemicals in the brain. For the last three decades it has been well known that one of the brain's systems—dopamine—is particularly involved. The main improvement in the last 20 years has been that we can now image these abnormalities in patients, their relatives, and in healthy individuals. This allowed us to revise understanding of the role of dopamine abnormalities in schizophrenia.
In particular, it allowed us to propose how some of the social stressors, drugs, and genetic abnormalities may all come together to cause abnormality in dopamine. And how this abnormality in dopamine, by altering the patient’s experience of their environment, leads to delusions and hallucinations.
How did you become involved in this research, and
how would you describe the particular challenges, setbacks, and
successes that you've encountered along the way?
I (Shitij Kapur) became involved in studying dopamine in schizophrenia almost two decades ago when doing my Fellowship at the University of Toronto—largely through the influence of professors Phil Seeman and Robert Zipursky. Since then it has been a major focus of my work through imaging the dopamine system.
However, this review article was not just about my work. In fact, we decided to write this because Dr. Oliver Howes and his team have made some recent important discoveries about exactly where in the dopamine system the abnormality is. His data showed that the major changes were presynaptic rather than postsynaptic and predated the onset of the illness.
We thought this was a good time to bring all the findings together than cast them into the Version III of the Dopamine Hypothesis of Schizophrenia. We called it Version III, because it is a continuation of one of the most productive neurochemical theories in psychiatry.
Where do you see your research leading in the
future?
The two most exciting avenues are linking the dopamine finding to psychosocial variables and looking for new therapeutic options. So, from the sociobiological view point we now know that early exposure to adversity, social stress, social defeat, and urbanicity all lead to greater incidence of psychosis.
Also there is preclinical evidence that animals exposed to analogous conditions show dopamine abnormalities. It will be very satisfying if one could test whether this is indeed the case in patients who go on to develop schizophrenia.
Regardless of how it comes about—once patients are psychotic they tend to show high levels of dopamine synthesis and dopamine levels. The recent research has made it clearer that this abnormality arises predominantly on the presynaptic side, while most of our treatments act on the post-synaptic side. So, this is a clear new possibility in therapeutics—to address the presynaptic dopamine system.
Do you foresee any social or political
implications for your research?
We don’t think our research has any direct social or political
implication—it is a rather straightforward neurochemical review.
However, the fact that social and psychological factors can lead to changes
in the brain chemistry is an intriguing idea with interesting implications
for society.
Professor Shitij Kapur
Dean and Head of School
Institute of Psychiatry
King's College London, UK
Oliver D. Howes, B.M., B.Ch., M.A., M.R.C.Psych.,
D.M.
Group Head
Consultant Psychiatrist/Senior Clinical Lecturer
Institute of Psychiatry
King's College London
University of
London
And
MRC CSC Psychiatric Imaging Group
Imperial College
Hammersmith Hospital
London, UK
ADDITIONAL INFORMATION:
- Read a December 2009 Fast Breaking Paper commentary by Oliver D. Howes.
KEYWORDS: PSYCHOSIS; BIOLOGY; ETIOLOGY; CAUSE; BRAIN; IMAGING; PATHOPHYSIOLOGY; RISK FACTORS; TREATMENT, POSITRON-EMISSION-TOMOGRAPHY; DOUBLE-BLIND PET; SCHIZOTYPAL-PERSONALITY-DISORDER; MEDIAL PREFRONTAL CORTEX; IN-VIVO BINDING; RECEPTOR-BINDING; OBSTETRIC COMPLICATIONS; NUCLEUS-ACCUMBENS; ANTIPSYCHOTIC-DRUGS; CLINICAL-RESPONSE.