A BRAIN imaging study has revealed that changes in dopamine production are directly linked to positive psychotic symptoms, regardless of whether patients are diagnosed with schizophrenia, bipolar disorder or major depression. The results could transform clinical approaches to mood-related psychosis.
Researchers have long known that dopamine plays a central role in psychosis, but most medical treatments target specific diagnostic categories such as schizophrenia. This new 18F-DOPA PET study, conducted by teams at Imperial College London, the University of Oxford and King’s College London, suggests that the underlying biology is not confined to traditional labels, opening the door to more targeted and personalised therapies for people experiencing psychosis alongside mood symptoms.
The study involved 76 participants, with 38 experiencing their first episode of psychosis (25 with depression, 13 with mania or mixed symptoms) and 38 healthy controls. PET scans measured dopamine synthesis capacity (Kicer) in three brain regions. Across all diagnostic groups, greater dopamine synthesis in the associative region was correlated with more severe hallucinations or delusions. Specifically, those with manic psychosis had higher dopamine activity in the limbic region compared with those whose psychosis included depression, while non-affective psychosis was linked to changes in the associative region. Overall, people with depressive symptoms and psychosis had significantly lower dopamine synthesis than those with mania, and the largest differences were found in the limbic striatum. These findings persisted even when controlling for age and sex.
Clinicians should consider the biological diversity of psychotic symptoms across different mood disorders when recommending treatment. While antipsychotic drugs commonly target the dopamine system, this study suggests their use may be relevant for a wider group of patients beyond those with a classic schizophrenia diagnosis.
Reference
Jauhar S et al. Dopamine and mood in psychotic disorders: an 18F-DOPA PET study. JAMA Psychiatry. 2025;DOI:10.1001/jamapsychiatry.2025.1811.
