Patients with schizophrenia who fail to respond to antipsychotic medications may have something in common — they appear to have normal levels of the neurotransmitter dopamine.
Schizophrenia is typically associated with an overactive dopamine system, which means that the brain is processing abnormally high levels of dopamine.
Traditional antipsychotic drugs attempt to normalize this process by blocking dopamine.
However, about one-third of individuals with schizophrenia do not respond to this treatment, and until now, no study has focused on whether dopamine abnormality is present in patients resistant to antipsychotic treatment.
“Despite considerable scientific and therapeutic progress over the last 50 years, we still do not know why some patients with schizophrenia respond to treatment whilst others do not.
“Treatment resistance in such a disabling condition is one of the greatest clinical and therapeutic challenges to psychiatry, significantly affecting patients, their families and society in general,” said researchers from King’s College London’s Institute of Psychiatry.
“Our findings suggest that there may be a different molecular mechanism leading to schizophrenia in patients who do not respond to anti-psychotic medication. Identifying the precise molecular pathway particularly in these patients is of utmost importance and will help inform the development of much-needed novel treatments,” they added.
For the study, the researchers used PET scan imaging to investigate dopamine synthesis capacity in 12 patients with schizophrenia who did not respond to treatment, 12 who did, and 12 healthy controls.
The results showed that schizophrenia patients whose illness was resistant to antipsychotic treatment have relatively normal levels of dopamine synthesis capacity. This would explain why the dopamine-blocking antipsychotic medication was not effective in this group.
However, researchers say that the findings need to be confirmed in larger samples before the study can affect clinical practice.
They add that future research will have to center around patients who have never taken antipsychotics in order to see whether presynaptic dopamine regulation was normal in patients in the treatment-resistant group at the beginning of the disorder, before any exposure to antipsychotic drugs.
Source: American Journal of Psychiatry