Increased dopamine synthesis – a feature classically associated with schizophrenia – might underlie bipolar psychosis, a new study suggests.
To conduct the cross-sectional case-control study, Sameer Jauhar, MRCPsych, and his associates recruited 60 people from first-episode psychosis services in London – 22 with bipolar psychosis, 16 with schizophrenia, and 22 matched controls. Of the 22 with bipolar psychosis, 18 were antipsychotic-naïve or free, and of the 16 patients with schizophrenia, 14 were antipsychotic-naïve (JAMA Psychiatry. 2017 Oct 11.). The researchers used fluorodihydroxyphenyl-L-alanine ([18F]-DOPA) positron emission tomography to study dopamine synthesis capacity in the participants.
The study showed that mean dopamine synthesis capacity in the striatum was significantly higher both in the bipolar group and the schizophrenia group, compared with controls – even after excluding individuals taking antipsychotic medication.
“These results extend previous findings that dopamine synthesis capacity is elevated in schizophrenia and psychosis associated with temporal lobe epilepsy and increases with the onset of psychosis, suggesting that presynaptic dopamine dysfunction is associated with psychosis across diagnostic categories,” wrote, who is affiliated with the Institute of Psychiatry, Psychology & Neuroscience at King’s College, London, and his coauthors.
In addition, Dr. Jauhar and his coauthors found a significant relationship between mean whole striatal dopamine synthesis capacity and Positive and Negative Syndrome Scale () scores in the group of patients who was experiencing a psychotic episode at the time of the study, which overall explained 27% of the variance.
In the bipolar disorder group, there was a nonsignificant relationship between whole striatal dopamine synthesis capacity and the PANSS positive subscale symptom severity score. However, this became significant when the analysis was restricted to patients who were experiencing a current psychotic episode and accounted for 36% of the variance in psychotic symptoms.
But this effect was not seen in patients with schizophrenia – all of whom were experiencing a psychotic episode at the time.
“Our finding of a relationship between positive psychotic symptoms and dopamine synthesis capacity in the combined bipolar and schizophrenia sample but not in the schizophrenia group could be due to a lack of power or inclusion of more patients with longer illness durations in the schizophrenia group,” the researchers reported.
Overall, no significant difference was found in mean dopamine synthesis capacity between patients with bipolar disorder and those with schizophrenia.
The authors also controlled for duration of illness, given that those in the schizophrenia group had a longer duration of illness than those in the bipolar group, with no effect on mean dopamine synthesis capacity differences between the two. The effect was seen in the whole striatum, the associative striatum, the limbic striatum, and the sensorimotor striatum.
“Relative to controls, the subregional analyses showed significant elevations in all three functional striatal subdivisions in the bipolar group but only a suggestion in the associative striatum in the schizophrenia group, with no differences in the substantia nigra for either group,” the authors wrote.
The authors acknowledged one concern with using patients experiencing a first episode of psychosis was that their diagnoses may change over time. But even after a minimum of 18 months’ follow-up, none of the original diagnoses had changed, and they had even been strengthened by the difference in negative but not positive symptoms.
The outcome measure used – KiCER – was an index for the uptake of [18F]-DOPA into dopamine neurons, and its conversion into [18F]-dopamine and storage in terminals. “Therefore, the increased KiCER we report likely reflects an increase in one or more of these processes, as well as a net increase in dopamine synthesis capacity,” they wrote.
“This finding provides a potential neurobiological explanation for why antipsychotic drugs, which are all dopamine D2/D3 receptor blockers, are effective in bipolar psychosis and schizophrenia and identifies the regulation of dopamine synthesis as a potential novel drug target for bipolar disorder and schizophrenia.” Furthermore, they said, the findings suggest that dopamine synthesis capacity might be a drug target for bipolar disorder and schizophrenia.
The study was supported by several entities, including the Medical Research Council, the U.S. Brain & Behavior Research Foundation, the Wellcome Trust, and the National Institute for Health Research Biomedical Research Centre at South London. Three authors declared research funding, advisory or speaker engagements, or lecture payments from a variety of pharmaceutical companies. No other conflicts of interest were declared.