Presynaptic Striatal Dopamine Dysfunction in People at Ultra-high Risk for Psychosis: Findings in a Second Cohort

• Published in: Biological psychiatry (1969) Vol. 74; no. 2; pp. 106 - 112
• Main Authors: Egerton, Alice, Chaddock, Christopher A., Winton-Brown, Toby T., Bloomfield, Michael A.P., Bhattacharyya, Sagnik, Allen, Paul, McGuire, Philip K., Howes, Oliver D.
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.07.2013; Elsevier
• Subjects: Adult; Adult and adolescent clinical studies; Basal Ganglia - diagnostic imaging; Biological and medical sciences; Cohort Studies; Corpus Striatum - diagnostic imaging; Dihydroxyphenylalanine - analogs & derivatives; Dopamine; Dopamine - biosynthesis; Female; Humans; imaging; Male; Medical sciences; positron emission tomography; Presynaptic Terminals - chemistry; Presynaptic Terminals - diagnostic imaging; Prodromal Symptoms; Psychiatric/Mental Health; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Psychoses; psychosis; Psychotic Disorders - diagnosis; Psychotic Disorders - diagnostic imaging; Radionuclide Imaging; Risk Factors; Schizophrenia; striatum; Young Adult; Dopamine; schizophrenia; striatum; positron emission tomography; imaging; psychosis; Radionuclide study; High risk; Central nervous system; Schizophrenia; Basal ganglion; Corpus striatum; Catecholamine; Encephalon; Psychosis; Imaging; Risk factor; Neurotransmitter; Positron emission tomography; Prepsychotic state; Emission tomography
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2012.11.017

Using positron emission tomography (PET), we previously observed increases in 3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine (18F-DOPA) uptake in the striatum of subjects at ultra-high risk (UHR) for psychosis, indicating elevated presynaptic dopamine synthesis capacity. The purpose of this study was to test if this finding would be replicated in a second UHR cohort. 18F-DOPA PET was used to estimate dopamine synthesis capacity in the striatum of an entirely new cohort of 26 individuals at UHR for psychosis (14 males, mean±SD age = 22.7±4.7 years) and 20 healthy volunteers matched for age and gender (11 males, mean±SD age = 24.5±4.5 years). Dopamine synthesis capacity was elevated in the whole [t(44) = 2.6; p = .01, effect size = .81] and associative striatum [t(44) = 2.6; p = .01, effect size = .73] of UHR compared with control subjects. When the two samples were combined to give a final sample of 32 control and 50 UHR subjects, the higher levels of dopamine synthesis capacity in the UHR group reached significance across the whole [F(1,81) = 11.0; p = .001], associative [F(1,81) = 12.7; p = .001], and sensorimotor [F(1,81) = 4.7; p = .03], but not the limbic [F(1,81) = 2.1; p = .2], striatum. The findings indicate that elevated dopamine synthesis capacity in the dorsal striatum is a robust feature of individuals at UHR for psychosis and provide further evidence that dopaminergic abnormalities precede the onset of psychosis.