Is striatal dopamine elevated in Individuals at risk for psychosis? Biol.Psych.July 2013.

19.07.2013

Many studies have shown that (using either 18F DOPA uptake or competition studies between endogenous DA and DA D 2 receptor ligands) Schizophrenia is associated with increases in striatal presynaptic DA function, at least during the period of psychotic exacerbation, and that this increase is associated with the severity and acuity of psychotic symptoms.  Increase in presynaptic dopamine  function is consistently shown in studies with a large effect size (0.8).Magnitude of this change is more in first and acute stages. Do individuals in prodromal psychotic state (UHR: Ultra High Risk for psychosis : 30-40% will develop psychosis in 2-3 years) also show these changes?

Alice Egerton ( Institute of Psychiatry, London) and team have previously shown that presynaptic dopamine synthesis capacity is increased in the striatum of UHR individuals and that these elevations are directly correlated with prodromal symptom severity. Progression to psychosis  in the UHR group  was influenced by the degree of elevation. ie changes in dopamine system preceded psychotic state and it could predict who will develop psychosis in the UHR group.  This idea has huge implications as it offer an opportunity for considering strategies for preventing the progress to psychosis. The group is now reporting the results from a new cohort and thus increase the statistical power of these observations.

Twenty-six UHR individuals and 20 controls participated in this.Most of the subjects were medication-free at the time of scanning.  Psychopathology was assessed using the Comprehensive Assessment of At-Risk Mental State (CAARMS). They underwent 18F-DOPA PET Imaging.

Findings

1.Striatal dopamine synthesis capacity was elevated in individuals at UHR for psychosis relative to matched healthy volunteers  with an effect size 0.8.

2.There were no relationship between symptom severity and elevation. It is possible that this relationship will become more apparent later on as progressive increase in striatal dopamine synthesis capacity happens  with the onset of psychosis.

Conclusions

Presence of elevated dopamine synthesis capacity before the onset of psychosis suggests that dopaminergic interventions may be useful in this phase of the disorder. Predictive value of this elevation needs to be seen in follow-up of this cohort.

Comment: In the accompanying commentary  Marc Laruelle  suggest that interventions that can negatively modulate the firing of DA cells might be useful.  Such light presynaptic modulation may not be as effective as D2 blockade during acute psychotic episodes, it might constitute an improved therapeutic intervention for the maintenance of remission and maybe for the prevention of first episode in UHR subjects.

Summary of the article:

Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for PsychosisFindings in aSecond Cohort.

Egerton A, Chaddock CA, Winton-Brown TT, Bloomfield MA, Bhattacharyya S, Allen P, McGuire PK, Howes OD. Biol Psychiatry. 2013 Jul 15;74(2):106-12

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