your views on schizophrenia and "aberrant salience"?

[ClinPsycMasters]

from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2635536/

"Most recently, Kapur (2003) proposed that the positive symptoms of schizophrenia may arise out of ‘the aberrant assignment of salience to external objects and internal representations’, and that antipsychotic medications reduce positive symptoms, by attenuating aberrant motivational salience, via blockade of the dopamine D2 receptor."

"A corollary of this is that antipsychotic medications will also necessarily attenuate adaptive motivational salience, that is the correct assignment of salience. This may result not only in positive symptom remission, but also negative side-effects related to loss of motivation, such as apathy and anhedonia."

The study referred to is the seminal work by Kapur:

Kapur S. Psychosis as a state of aberrant salience: a framework linking biology, phenomenology, and pharmacology in schizophrenia. American Journal of Psychiatry. 2003;160:13–23.

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[hippiedoc13]

I read this early in my first year of residency and it was very influential in shaping the way I conceptualize psychosis. Personally I thought it was brilliant. Now I regularly pass it around to other residents and to particularly bright medical students on my service when the topic of psychosis comes up.

 

[ClinPsycMasters]

I want to add that another recent paper on schizophrenia makes for an interesting and informative read:

Howes OD, Kapur S. The dopamine hypothesis of schizophrenia: version
III—the final common pathway. Schizophr Bull. 2009;35:549–562.

Here's a taste for those who haven't read it:

"we hypothesize that multiple "hits" interact to result in dopamine dysregulation—the final common pathway to psychosis in schizophrenia...Second, the locus of dopamine dysregulation moves from being primarily at the D2 receptor level to being at the presynaptic dopaminergic control level."

"Firstly, it implies that current antipsychotic drugs are not treating the primary abnormality and are acting downstream. While antipsychotic drugs block the effect of inappropriate dopamine release, they may paradoxically worsen the primary abnormality by blocking presynaptic D2 autoreceptors, resulting in a compensatory increase in dopamine synthesis. There is some evidence from healthy volunteers that acute antipsychotic treatment does increase presynaptic dopamine synthesis capacity, and while successful subacute treatment can reduce this, it is nevertheless elevated in patients who have received antipsychotic treatment for many years. This may explain why patients relapse rapidly on stopping their medication, and if the drugs may even worsen the primary abnormality, it also accounts for more severe relapse after discontinuing treatment. This suggests that drug development needs to focus on modulating presynaptic striatal dopamine function, either directly or through upstream effects."

 

[strangeglove]

This is an interesting theory, though it is shoehorning schizophrenia into Robinson and Berridge's incentive sensitization theory of addiction. This is a theory of dopamine action in the striatum, and explains how stimuli associated with drug use gain "salience" through sensitization of a neural system for "wanting" that includes the ventral striatum.

 

[whopper]

The study is interesting because it is quite apparent that schizophrenics (especially those with disorganized type) don't seem to learn quite as fast. IMHO, (and this is only a hypothesis), if the tester were to get more specific schizophrenics (e.g. down to the type of schizoprenia) he might get differing results.

As for the dopamine theories mentioned above, a lot of what is likely going on suggests the medications we give are working up or downstream in relation to the actual pathology.

 

[Ibid]

As for the dopamine theories mentioned above, a lot of what is likely going on suggests the medications we give are working up or downstream in relation to the actual pathology.

The actual pathology may not even be "in" the stream. Don't forget that.

This is an interesting theory, though it is shoehorning schizophrenia into Robinson and Berridge's incentive sensitization theory of addiction.

Indeed.

To the original question:

"Most recently, Kapur (2003) proposed that the positive symptoms of schizophrenia may arise out of ‘the aberrant assignment of salience to external objects and internal representations',

A delusion, an image in the visual cortex that has no correlate in the outside world, a sound that isn't there, a smell, all these internal represetations of things that don't exist, if they are given any salience at all then that salience would a priori be aberrant.

That is the fundamental flaw with this theory. Interesting reading but in my opinion not the best way to conceptualise psychosis and certainly trying to shoehorn it into a pathway seems of limited utility. Of course the author is attempting a unfied theory but in my own opinion given the state of the art so to speak, that is premature.

One more thought.

This may explain why patients relapse rapidly on stopping their medication, and if the drugs may even worsen the primary abnormality, it also accounts for more severe relapse after discontinuing treatment.

If the drug has worsened the primary abnormality (not my first choice of words but never mind) then relapse is not really the right word. That is what is know as an iatrogenic effect. Tut Tut to the author.....

Interesting though.