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News Brief: Normal Dopamine Synthesis Capacity in Treatment-Resistant Schizophrenia

Treatment-resistant schizophrenia patients have a lower dopamine synthesis capacity than individuals who respond to antipsychotics, according to a new study published online October 3 in the American Journal of Psychiatry and led by Arsime Demjaha of King’s College London. The dopamine synthesis capacity of treatment-refractive subjects was comparable to that of healthy subjects, suggesting that dopamine-blocking antipsychotic drugs are only effective in those patients who have an elevated dopamine synthesis capacity.

Several studies have reported increased striatal dopamine synthesis capacity in schizophrenia using positron emission tomography (PET) (see SRF related news story). Unfortunately, approximately one third of schizophrenia patients show a limited response to antipsychotic treatment (Lindenmayer, 2000), but just how the hyperdopaminergic state relates to the response to antipsychotics remains unclear.

In the current study, Demjaha and colleagues examined striatal dopamine synthesis capacity in 12 treatment-resistant and 12 treatment-responsive schizophrenia subjects, as well as in 12 healthy controls. They found that dopamine synthesis capacity was elevated in the treatment-responsive subjects, but not in the treatment-resistant subjects or in healthy controls. The elevation was most prominent in the associative and limbic striatal subdivisions.

This finding may explain why symptoms in some patients are not improved with antipsychotics. According to the authors, their data suggest that “patients with treatment-resistant illness start with a different underlying pathophysiology or that antipsychotics have an effect on their dopamine synthesis capacity, albeit one that does not reduce symptoms.” Importantly, since all subjects in the current study were medicated, future studies will need to examine antipsychotic-naïve subjects.—Allison A. Curley.

Demjaha A, Murray RM, McGuire PK, Kapur S, Howes OD. Dopamine Synthesis Capacity in Patients With Treatment-Resistant Schizophrenia. Am J Psychiatry. 2012 Oct 3. Abstract

Comments on News and Primary Papers

Primary Papers: Dopamine Synthesis Capacity in Patients With Treatment-Resistant Schizophrenia.

Comment by:  Jeffrey Lieberman, SRF Advisor
Submitted 9 October 2012
Posted 9 October 2012
  I recommend this paper

This interesting result is consistent with prior work by Abi-Dargham and Laruelle, and with prevailing hypotheses. A question is whether the treatment-resistant patients represent a stable phenotype or evolved to this in the course of their illness. In this context, it would be useful to know where in the course of their illness the patients were, and whether they were previously treatment responsive or not.

View all comments by Jeffrey Lieberman

Comments on Related News

Related News: Schizophrenia Genetics 2015—Part 5, Plan of Action

Comment by:  Robert Peers
Submitted 4 September 2015
Posted 6 September 2015

I often wonder why schizophrenia researchers do not look for the genes that cause schizotaxia, since this non-psychotic cognitive/anhedonic disorder may underlie schizophrenia—and apparently can be seen in close relatives of schizophrenia patients.

View all comments by Robert Peers