Dopamine synthesis increased in patients at high risk for psychosis

UK study results show that patients at ultra-high risk (UHR) for psychosis have elevated dopamine synthesis capacity in the dorsal striatum.

The current findings confirm those from a previous study of 24 UHR patients and 12 mentally healthy controls, suggesting that "dopaminergic interventions may be useful in this phase of the disorder," say Alice Egerton (King's College London) and colleagues.

For the current study, the researchers recruited 26 individuals (14 men), aged an average of 22.7 years, at UHR for psychosis and 20 age- and gender-matched mentally healthy controls.

All of the UHR patients had attenuated psychotic symptoms, such as abnormal beliefs, perceptions, or speech. Additionally, four had experienced at least one brief, spontaneously remitting psychotic episode lasting less than 1 week in the previous year, six had a first-degree relative with schizophrenia, and two met DSM-IV criteria for schizotypal personality disorder.

The participants were assessed for 3,4-dihydroxy-6-fluoro-L-phenylalanine (18F-DOPA) uptake in the striatum using positron emission tomography.

The researchers found that UHR patients had increased dopamine synthesis capacity in the whole striatum compared with controls.

When analysis was restricted to functional striatal subdivisions, the elevation in dopamine synthesis capacity among UHR patients relative to controls was significant in the associative subdivision, and showed trend level significance in the sensorimotor subdivision. There was no significant between-group difference in dopamine synthesis capacity in the limbic striatum, however.

These differences remained true after accounting for the use of antipsychotic medications and other drugs.

When data from the previous and current study were combined, the team found that the elevation in dopamine synthesis capacity among UHR patients compared with controls, after accounting for scanner effects, was significant in the whole striatum, the associative subdivision, and the sensorimotor subdivision, but not in the limbic striatum.

Egerton and team conclude in Biological Psychiatry: "This study confirms that striatal dopamine synthesis capacity, as indexed by 18F-DOPA uptake, is elevated in people at UHR for psychosis."

They add: "Clinical follow-up of our first cohort found that those UHR subjects with the highest levels of striatal 18F-DOPA uptake at presentation were the most likely to develop a psychotic disorder over the next 3 years.

"Clinical follow-up of this second cohort will confirm whether the extent of dopaminergic elevation at baseline is predictive of subsequent onset of psychosis."

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