Dopamine dysfunction underlies the pathoetiology of psychosis in both bipolar disorder and schizophrenia, according to a study by Sameer Jauhar, MRCP of the Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience at King’s College, London, England, and colleagues published in JAMA Psychiatry.
Dopamine synthesis capacity was significantly elevated in both disorders, suggesting a potential novel drug target for bipolar disorder and schizophrenia in this cross-sectional case-control positron emission tomographic (PET) study.
The researchers recruited patients from first-episode psychosis services in inner-city London, United Kingdom, and included 60 subjects in the study: 22 with bipolar psychosis, 16 with schizophrenia, and 22 controls. Of the patients with bipolar psychosis, 18 were antipsychotic-naïve or -free, as were 14 of the patients with schizophrenia.
All participants underwent fluorodihydroxyphenyl-L-alanine ([18F]-DOPA) PET scan to evaluate dopamine synthesis capacity. Clinical measures included the Positive and Negative Syndrome Scale, the Young Mania Rating Scale, and the Global Assessment of Functioning.
Striatal dopamine synthesis capacity (Kicer) was significantly elevated in both the bipolar group and the schizophrenia group compared with controls, but there was no significant difference between the bipolar and schizophrenia groups. Furthermore, Kicer showed a significant positive correlation with positive psychotic symptom severity. In the combined bipolar-schizophrenia group, elevated Kicer explained 27% of the variance in psychotic symptoms, and in the bipolar group it explained 36%. This relationship was not observed in the schizophrenia group alone, but this may be due to a lack of power or the inclusion of patients with longer illness duration.
A potential limitation of the study was the lack of a nonpsychotic bipolar disorder control group. The study also was not designed or powered to detect a difference between bipolar psychosis and schizophrenia. Although a small number of individuals were taking antipsychotic medication, which may have effects on dopamine, Kicer remained significantly elevated even when the analysis was restricted to patients who were antipsychotic-naïve or -free.
The investigators concluded that the regulation of dopamine synthesis is a potential drug target for both bipolar disorder and schizophrenia.
Jauhar S, Nour MM, Veronese M, et al. A test of the transdiagnostic dopamine hypothesis of psychosis using positron emission tomographic imaging in bipolar affective disorder and schizophrenia [published online October 11, 2017]. JAMA Psychiatry. doi:10.1001/jamapsychiatry.2017.2943