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Clinical Psychochemistry
Dopamine Dysfunction and Delusions, Hallucinations and Anhedonia
Graham Murray
Senior Clinical Research Associate, Department of Psychiatry, University of Cambridge
Abstract
This article outlines theoretical arguments along with related empirical studies concerning the relationship between abnormal reward
processing and the symptoms of schizophrenia. Patients with schizophrenia and other psychoses usually show behavioural and
physiological abnormalities when learning about or anticipating rewards or other important events. Patients also show impaired ability to
modulate behaviour in response to incentives. There are plausible theories to directly link these abnormalities to the manifestation of
positive and negative psychotic symptoms, but to date these links remain theoretical.
Keywords
Reward, psychosis, schizophrenia, dopamine, learning
Disclosure: Graham Murray is supported by the Medical Research Council and the National Alliance for Research on Schizophrenia and Depression (NARSAD).
Acknowledgements: This article stems from collaborative work over several years with Paul Fletcher, Phil Corlett and colleagues.
Received: 3 November 2008 Accepted: 30 March 2009
Correspondence: Graham Murray, Department of Psychiatry, University of Cambridge, Box 189 Addenbrooke’s Hospital, Cambridge, CB2 0QQ, UK. E: gm285@cam.ac.uk
In this article I will draw on a selection of recent evidence to advance an to consider the role of the system in question in health. Evidence over
argument that attempts to relate dopamine dysfunction to both positive the last 30 years has shown that ascending midbrain dopamine
and negative symptoms of schizophrenia (and other mental illnesses) neurons (mesocorticolimbic or mesostriatal) play a key role in
via disruption of its normal role in motivation and learning about learning about reward, signalling errors in the prediction of reward
rewards. The argument itself is not new, but very recent functional and motivational processing.
8–11
It is therefore not surprising that
magnetic resonance imaging (fMRI) and behavioural neuropsychological some authors have proposed that dopamine abnormalities lead to
evidence has emerged to support it; herein I will present this new symptoms of schizophrenia because of disruptions in dopamine’s role
evidence in relation to the previously established theoretical position. in motivational and reward processing. Indeed, both motivational
deficits and dysfunction of associative learning (closely related to
Extensive evidence from molecular imaging studies implicates reward learning) were proposed in schizophrenia long before the
dysregulated striatal dopamine in schizophrenia, and very recent discovery of dopamine. For example, Bleuler described avolition and
evidence suggests that such abnormalities may be generalisable to the loosening of associations (due to a failure of any unifying concept of
earliest stages of psychotic illness.
1–4
Although Laruelle and colleagues purpose or goal) as core features of schizophrenia.
12
have shown that the degree of sensitisation of the dopamine system is
linked to the severity of psychotic symptoms, it remains unclear how the In the early 1970s, Stein and Wise proposed that dysfunction of
subjective experience of illness emerges from this underlying biological monoamine neurotransmission could explain both of the core
disturbance. For example, we know that dopamine is important for schizophrenia deficits: avolition and loosening of associations.
13
In
movement, and perhaps also for mood.
5
So, why does dopamine advancing this argument, they drew on early evidence that noradrenalin
dysfunction in psychotic illness lead to paranoia and not to some other (not dopamine) mediated these reward-related process. They reasoned
manifestations, such as motor disturbance or mood disturbance? We that because noradrenalin (as was thought at the time) is important in
should aim to understand how brain disturbances lead to symptoms both motivation and learning of goal-directed associations, perhaps
through intermediate psychological processes that are more clearly dysfunction of this one system could explain both of these features of
related to biology;
6,7
only then will we be able to answer the question of the disorder. However, as the majority of evidence subsequently
how a neurotransmitter disturbance has anything to do with paranoia, demonstrated the primacy of dopamine (as opposed to noradrenalin) in
hallucinations or anhedonia, and how and why a dopamine D
2
receptor reward and motivational processing (and as extensive data
antagonist can improve such symptoms. accumulated implicating dopamine dysfunction in schizophrenia), the
argument was subsequently re-formulated by a number of successive
Dopamine’s Role in Health and authors. Some scholars focused their arguments on delusions and
Psychiatric Disease hallucinations,
14–17
some on stereotyped thought and behaviour
18
In order to understand how dysfunction of a neurotransmitter system and some on negative symptoms.
19
In most of these re-formulated
may lead to psychiatric manifestations, a straightforward strategy is models, the emphasis is on dopamine instead of noradrenalin, although
© TOUCH BRIEFINGS 2009 21