Journal
MOLECULAR PSYCHIATRY
Volume 24, Issue 10, Pages 1502-1512Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41380-018-0042-4
Keywords
-
Funding
- AstraZeneca
- BMS
- Eli Lilly
- Jannsen-Cilag
- Roche
- Medical Research Council, UK
- Wellcome Trust [094849/Z/10/Z]
- GlaxoSmithKline
- Medical Research Council [MC-A656-5QD30]
- Maudsley Charity grant [666]
- US Brain & Behavior Research Foundation
- National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust
- JMAS SIM Fellowship from the Royal College of Physicians, Edinburgh
- King's College London
- MRC [MC_U120097115, MR/N026063/1, G1100809] Funding Source: UKRI
Ask authors/readers for more resources
Psychotic illnesses show variable responses to treatment. Determining the neurobiology underlying this is important for precision medicine and the development of better treatments. It has been proposed that dopaminergic differences underlie variation in response, with striatal dopamine synthesis capacity (DSC) elevated in responders and unaltered in nonresponders. We therefore aimed to test this in a prospective cohort, with a nested case-control comparison. 40 volunteers (26 patients with first-episode psychosis and 14 controls) received an F-18-DOPA Positron Emission Tomography scan to measure DSC (Ki(cer)) prior to antipsychotic treatment. Clinical assessments (Positive and Negative Syndrome Scale, PANSS, and Global Assessment of Functioning, GAF) occurred at baseline and following antipsychotic treatment for a minimum of 4 weeks. Response was defined using improvement in PANSS Total score of >50%. Patients were followed up for at least 6 months, and remission criteria applied. There was a significant effect of group on Ki(cer) in associative striatum (F-(2,F- 37) = 7.9, p = 0.001). Ki(cer) was significantly higher in responders compared with non-responders (Cohen's d =1.55, p = 0.01) and controls (Cohen's d= 1.31, p = 0.02). Ki(cer) showed significant positive correlations with improvements in PANSS-positive (r = 0.64, p < 0.01), PANSS negative (rho = 0.51, p = 0.01), and PANSS total (rho = 0.63, p < 0.01) ratings and a negative relationship with change in GAF (r = -0.55, p < 0.01). Clinical response is related to baseline striatal dopaminergic function. Differences in dopaminergic function between responders and non-responders are present at first episode of psychosis, consistent with dopaminergic and non-dopaminergic sub-types in psychosis, and potentially indicating a neurochemical basis to stratify psychosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available