The findings of a new brain study could change the way doctors treat mood disorders involving psychosis in patients.
The brain imaging study found that changes in brain dopamine are linked to the presence of psychotic symptoms, no matter whether a person has been diagnosed with schizophrenia, bipolar disorder, or major depression.
The research, published in JAMA Psychiatry by teams at Imperial College London, the University of Oxford and King's College London, suggests that the underlying biological basis of psychosis doesn't correspond to traditional diagnostic labels.
The researchers used PET scanning to examine the brains of people who were experiencing their first episode of psychosis alongside other mood disorders involving either depressive or manic symptoms, to measure how much dopamine the brain made.
Across both diagnostic groups scanned - mania and depression - increased dopamine synthesis was linked to positive psychotic symptoms, such as hallucinations or delusions.
This suggests that antipsychotic drugs, which target the dopamine system, can treat psychotic symptoms across diagnoses.
At present, most medical treatments for psychosis (antipsychotics) target dopamine, but are often given to only groups of people with particular psychotic disorders, e.g. schizophrenia. By contrast, people with depression and psychosis tend not to receive medicines targeting dopamine, owing to less research in this group.
Lead researcher Dr Sameer Jauhar at Imperial College London's Department of Brain Sciences said: "The diagnostic categories we use in psychiatry may not be the best guide to prescribing or predicting treatment response – the biology of psychosis is more nuanced. Essentially, Mother Nature does not read psychiatry classification systems, and neither should she have to. "
The study has implications for how common disorders involving psychosis are presently treated, with the prospect of more targeted treatments for groups in future.
The researchers scanned 76 people, 38 of whom had psychosis and mood symptoms (25 depression, 13 mania/mixed) and 38 healthy controls. They used PET scanners to measure dopamine production in three striatum brain regions; the associative, limbic and sensorimotor.
Among the key findings:
- Across all participants, higher dopamine synthesis (Kicer) in the associative striatum was correlated with greater severity of psychotic symptoms, independent of diagnostic category.
- Dopamine synthesis (Kicer) was higher in individuals with manic psychosis compared to those with psychosis and depression, especially in the limbic striatum.
- In contrast, individuals with non-affective psychosis showed greater involvement of the associative striatum.
- This suggests both shared and distinct dopaminergic mechanisms across different forms of psychosis.
Co-author Dr Rob McCutcheon of the University of Oxford said: "Most of our current treatments for psychosis work by modulating dopamine signalling, but we often use them in a one-size-fits-all way. This study shows that dopamine dysfunction isn't uniform in psychosis. If we want to move beyond trial-and-error prescribing, we need to match treatments to underlying biology."
The study was supported by the JMAS Fellowship from the RCP (Edinbrgh) Wellcome Trust, NIHR, Medical Research Council, and EU Horizon programmes.
Dopamine and Mood in Psychotic Disorders An 18F-DOPA PET Study is published in JAMA Psychiatry.
