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Study reveals potential drug target for bipolar disorder, schizophrenia

Recent findings suggested dopamine synthesis capacity as a potential drug target for bipolar disorder and schizophrenia.

“The dopamine hypothesis suggests that dopamine abnormalities underlie psychosis, irrespective of diagnosis, implicating dopamine dysregulation in bipolar affective disorder and schizophrenia, in line with the research domain criteria approach. However, this hypothesis has not been directly examined in individuals diagnosed with bipolar disorder with psychosis,” Sameer Jauhar, MRCPsych, of King’s College, London, and colleagues wrote.

To compare dopamine synthesis capacity in bipolar disorder with psychosis vs. schizophrenia and to determine if dopamine synthesis capacity is associated with psychotic symptom severity, regardless of diagnostic class, researchers conducted a cross-sectional case-control positron emission tomography study among 22 individuals with bipolar psychosis, 16 with schizophrenia and 22 matched controls. Study participants underwent fluorodihydroxyphenyl-L-alanine PET. Mean age ranged from 23.6 years to 26.3 years.

Striatal dopamine synthesis capacity was significantly higher in participants with bipolar psychosis and schizophrenia compared with controls, with no significant differences reported between bipolar psychosis and schizophrenia groups.

In a combined bipolar and schizophrenia sample of participants experiencing a psychotic episode, dopamine synthesis capacity positively correlated with positive psychotic symptom severity and explained 27% of variance in symptom severity (P = .003).

Dopamine synthesis capacity was positively associated with positive psychotic symptom severity among participants with bipolar disorder experiencing a current psychotic episode (P = .01). This association remained significant when adjusting for manic symptom severity.

In an accompanying editorial, Dost Öngür, MD, PhD, of McLean Hospital, Harvard Medical School, weighed the clinical relevance of the study findings.

“There is some empirical support for the notion that schizophrenia and bipolar disorder exist along a psychosis continuum, with some patients having more affective features and others having more psychotic features. On the other hand, the contribution by Jauhar and coauthors indicates that along one important dimension, that of dopaminergic dysfunction, schizophrenia and bipolar disorder are similar; there is a hint that change over time is what distinguishes them,” he wrote. “Clinical experience is perhaps more consistent with a model including not one but two dimensions, namely, affective and psychotic. ... In this framework, the abnormality reported by Jauhar and coauthors is associated with the psychosis dimension and could serve to quantify this dimension in future studies, advancing the research agenda toward ultimately developing a more valid classification system for psychotic disorders.” – by Amanda Oldt

Disclosures: Jauhar reports no relevant financial disclosures. Öngür reports serving on a scientific advisory board for Neurocrine Biosciences in 2017. Please see the study for all other authors’ relevant financial disclosures.