Dopamine in Psychosis: Are We on the Right Path?

Derick E. Vergne, MD


February 21, 2014

Dopaminergic Basis of Salience Dysregulation in Psychosis

Winton-Brown TT, Fusar-Poli P, Ungless MA, Howes OD
Trends Neurosci. 2014;37:85-89

Dopamine and Psychosis

As clinicians, we have some idea that dopamine has something to do with the onset of psychosis. We know this because of the historical concept that "blocking" dopamine receptors somehow improves some psychotic states.[1] We just don't know the "where" and "how." We give antipsychotics, which we understand to be "dopamine blockers," and the irrational becomes rational again.


In their article, Winton-Brown and colleagues present a general theory based on current data on the role of salience and dopamine in the potentiation of psychotic states. To get a sense of the role of salience in psychosis, we need to first grasp the meaning of "salience"; the putative role of dopamine dysfunction in disrupting salience; and how salience may affect our sense of the world, and thereby induce psychotic states.

Salience in cognitive neuroscience can be better understood as the act of "noticing" a stimulus among competing ones. In other words, we are constantly presented with multiple incoming stimuli in the form of what we experience in everyday life. Winton-Brown and colleagues refer to salience in the context of prioritizing, or "filtering," one experience over another, a process that his putatively mediated by dopamine through the basal ganglia (striatum). They make reference to the dimensions of salience -- eg, reward prediction, threat prediction, prediction error, emotional salience, novelty salience, and explicit salience attribution (outcome-relevant vs -irrelevant stimulus) to depict the role of the striatum and its microcircuitry in the processing and ultimate organization of diverse, yet related, stimuli.

This is supported by multiple lines of evidence on the action of the striato-pallidal-thalamic circuit connecting to prefrontal areas as key to the appropriate selective process of incoming stimuli to create a coherent version of reality.[2,3,4,5] Dopamine appears to be an active participant in this process.[6]

On the other hand, psychosis can be conceptualized as the aberrant processing of incoming stimuli, thereby inducing the experience of noncoherence. To that extent, the investigators cite some of the earlier authorities in phenomenology of psychiatry, Karl Jaspers among them, to refer to the experience of prodromal psychosis as a "general delusional atmosphere with all its vagueness of content."[3] The early great phenomenologists knew what biological psychiatrists are beginning to understand.


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