Neuroprotective effects of low-dose lithium in individuals at ultra-high risk for psychosis. A longitudinal MRI/MRS study.

OBJECTIVES: To investigate if low-dose lithium may counteract the microstructural and metabolic brain changes proposed to occur in individuals at ultra-high risk (UHR) for psychosis. METHODS: Hippocampal T2 relaxation time (HT2RT) and proton magnetic resonance spectroscopy ((1)H-MRS) measurements were performed prior to initiation and following three months of treatment in 11 UHR patients receiving low-dose lithium and 10 UHR patients receiving treatment as usual (TAU). HT2RT and (1)H-MRS percentage change scores between scans were compared using repeated measures ANOVA and correlated with behavioural change scores. RESULTS: Low-dose lithium significantly reduced HT2RT compared to TAU (p=0.018). No significant group by time effects was seen for any brain metabolites as measured with (1)H-MRS, although myo-inositol, creatine, choline-containing compounds and NAA increased in the group receiving low-dose lithium and decreased or remained unchanged in subjects receiving TAU. CONCLUSIONS: This pilot study suggests that low-dose lithium may protect the microstructure of the hippocampus in UHR states as reflected by significantly decreasing HT2RT. Larger scale replication studies in UHR states using T2 relaxation time as a proxy for emerging brain pathology seem a feasible mean to test neuroprotective strategies such as low-dose lithium as potential treatments to delay or even prevent the progression to full-blown disorder.

Multicentre prospective randomised trial of tacrolimus, azathioprine and prednisolone with or without basiliximab: two-year follow-up data.

A total of 192 children and adolescents undergoing renal transplantation were randomly chosen to receive tacrolimus, azathioprine and corticosteroids (TAS, n = 93) or tacrolimus, azathioprine, corticosteroids and two doses of basiliximab (TAS + B, n = 99). Six-month outcome data have previously been reported; this manuscript reports the 2-year data. Complete 2-year data were available on 164 (85.4%) of the original 192 patients. There was a single death in the TAS arm. Kaplan-Meier estimates of survival free of graft loss at 2 years were 94.9% in the TAS + B arm and 89.6% in the TAS arm [hazard ratio (HR) 0.52; 95% confidence interval (CI) 0.17 to 1.54, P = 0.23]. Estimates of survival free from rejection at 2 years were 75.2% in the TAS + B arm and 68.7% in the TAS arm (HR 0.81; 95% CI 0.46 to 1.40, P = 0.44). The mean estimated glomerular filtration rate (GFR) at 2 years, was 65.8 ml/min per 1.73 m(2) body surface area in the TAS arm and 66.7 ml/min per 1.73 m(2) in the TAS + B arm (P = 0.78). Blood pressure and cholesterol levels were similar in the two arms, and there was no evidence of a difference in the incidence of infection or malignancy. These data provide further evidence of a lack of benefit associated with the addition of basiliximab to a TAS regimen for European paediatric renal transplant recipients at low immunological risk.