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