Amphetamine-Induced Dopamine Release Predicts 1-Year Outcome in First-Episode Psychosis: A Naturalistic Observation.

BACKGROUND AND HYPOTHESIS: The dopamine theory of schizophrenia suggests that antipsychotics alleviate symptoms by blocking dopamine D2/3 receptors, yet a significant subset of patients does not respond adequately to treatment. To investigate potential predictors, we evaluated d-amphetamine-induced dopamine release and 1-year clinical outcomes in 21 antipsychotic-naive patients with first-episode schizophrenia. STUDY DESIGN: Twenty-one antipsychotic-naive patients (6 female) underwent dopamine D2/3 receptor radioligand [11C]-(+)-PHNO positron emission tomography. For estimating dopamine release, scans were performed with and without d-amphetamine pretreatment. The Positive and Negative Syndrome Scale was performed at regular intervals over 1 year while receiving treatment in a naturalistic setting (Clinical Trial Registry: EUDRACT 2010-019586-29). STUDY RESULTS: A group analysis revealed no significant differences in d-amphetamine-induced dopamine release between patients with or without clinically significant improvement. However, d-amphetamine-induced dopamine release in ventral striatum was significantly associated with reductions in positive symptoms (r = 0.54, P = .04; uncorrected P-values); release in globus pallidus correlated with a decrease in PANSS negative (r = 0.58, P = .02), general (r = 0.53, P = .04), and total symptom scores (r = 0.063, P = .01). Higher dopamine release in substantia nigra/ventral tegmental area predicted larger reductions in general symptoms (r = 0.51, P = .05). Post-amphetamine binding in putamen correlated positively with negative symptom scores at baseline (r = 0.66, P = .005) and throughout all follow-up visits. CONCLUSIONS: These exploratory results support a relationship between d-amphetamine-induced dopamine release and the severity and persistence of symptoms during the first year of psychosis.

Clinical relevance of circadian melatonin release in relapsing-remitting multiple sclerosis.

A growing body of evidence indicates the role of melatonin (MT) in the pathogenesis of multiple sclerosis (MS): It modulates immune function, alleviates oxidative stress and it is linked to seasonality of MS relapse. This report addresses the potential clinical relevance of circadian MT rhythms in relapsing-remitting MS (RRMS) patients. The study sample comprised of fifty-five RRMS patients and fifty age- and sex-matched healthy control (HC) subjects. Circadian salivary MT was measured non-invasively at 12 time points over day in participants' home environment. 6-Hydroxy-melatoninsulfate (MT sulfate) concentration in night-time urine was assessed as an estimate for nocturnal MT. Ratings for neurological disability, health-related quality of life (HrQoL), fatigue, depressive symptoms and sleep patterns were additionally obtained. There was no evidence for an overall disturbed MT rhythm in RRMS patients. However, lower MT levels within the first hour after awakening were associated with longer disease duration. MT levels only correlated moderately with neurological disability. Sleep disruptions were more common in patients than in controls and were associated with lower nocturnal MT sulfate levels. MT also correlated moderately with fatigue and HrQoL. We did not find evidence for a generally disturbed circadian MT rhythm in RRMS patients but longer disease duration was associated with significantly lower MT levels. Moreover, MT correlated with a series of clinical features. The exact nature of this relationship remains unclear and future studies are needed in order to determine whether MT could serve as a potential therapeutic target in MS. KEY MESSAGES: Melatonin acts as a free radical scavenger and modulates immune function. In multiple sclerosis, low melatonin levels were associated with acute exacerbations. Melatonin levels are not generally disturbed in multiple sclerosis patients. But lower levels are associated with disease duration and clinical aspects. Salivary melatonin after awakening might serve as a good measure of melatonin.