Brain scans have identified two previously unreported psychosis subtypes, suggesting structural differences may reflect separate illness mechanisms.
The findings suggest that variation in psychosis symptoms, treatment responses and long-term outcomes could reflect separate illness mechanisms and developmental pathways.
Researchers analysed structural brain scans from 381 people diagnosed with schizophrenia spectrum disorders or bipolar disorder with psychotic features, where psychotic symptoms occur only during episodes of mania or depression.
The team at Vanderbilt Health used an algorithm called similarity network fusion (SNF), which combines different brain scan measurements to identify people with similar patterns of structural abnormalities.
The analysis included measures of cortical thickness, cortical surface area and the volume of structures beneath the cerebral cortex.
It separated patients into two groups. Both included people with schizophrenia spectrum disorders and bipolar disorder with psychotic features, suggesting the structural patterns did not correspond directly with their clinical diagnoses.
One group showed enlargement of structures called the striatum within the basal ganglia. The striatum contains large numbers of dopamine receptors, and researchers said increased volume in this area may be attributed to excess dopamine signalling.
Most current antipsychotic medicines work by blocking dopamine receptors.
The second group had smaller volumes across the brain, including in the thalamus and hippocampus, structures consistently identified as abnormal in psychotic disorders.
The groups also showed contrasting changes in the cortex, the brain’s outer layer, which is involved in reasoning, speech, voluntary movement and processing sensory information.
The first group had moderately enlarged cortical surface areas, while surface area was markedly smaller in the second. People in the second group also had more severe negative symptoms, greater neuropsychological impairment and lower estimated intellectual functioning.
Using a brain atlas showing how different cell types are distributed across the cortex, researchers found that areas with smaller surface area in the second group overlapped with regions rich in layer 5 intratelencephalic neurons, cells involved in connections between areas of the cortex.
Neil Woodward, corresponding author and professor of psychiatry and behavioural sciences, said: “These data point to the fact that there are different pathophysiological processes that are happening here, and they are at least partially independent.”
He said the differences in cortical surface area “suggest there is something that went wrong in very early brain development. That’s where these two groups are starting to diverge.”
Woodward added that further study is needed, but said: “These findings may provide the foundation for more personalized approaches to diagnosing and treating psychiatric disorders.”
Both groups included young people who had experienced their first psychotic episode, and Woodward said he hopes to follow the research participants over time.
“If you are subtype 1, do you have a better outcome?” he asked. “Are you more responsive to medication? Does your cognition stay relatively normal?”
The research was supported by the National Institutes of Health, the Charlotte and Donald Test Fund, and the Vanderbilt Institute for Clinical and Translational Research.
