Neuroprotective Effects of Low-dose Lithium in Individuals at Ultra-high Risk for Psychosis. A Longitudinal MRI/MRS Study

Title: Neuroprotective Effects of Low-dose Lithium in Individuals at Ultra-high Risk for Psychosis. A Longitudinal MRI/MRS Study

Volume: 18 Issue: 4

Author(s): Gregor E. Berger, Stephen J. Wood, Margaret Ross, Clare A. Hamer, R. Mark Wellard, Gaby Pell, Lisa Phillips, Barnaby Nelson, G. Paul Amminger, Alison R. Yung, Graeme Jackson, Dennis Velakoulis, Christos Pantelis, Husseini Manji and Patrick D McGorry

Affiliation:

Keywords: Brain imaging, Lithium, Magnetic Resonance Imaging, Psychosis, (Indicated) Prevention, Neuroprotection, Ultra-High Risk (UHR), At Risk Mental State (ARMS), Hippocampal T2 relaxation time (HT2RT), proton magnetic resonance spectroscopy

Abstract: 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 (1H-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 1H-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 1H-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.

Cite this article as:

E. Berger Gregor, J. Wood Stephen, Ross Margaret, A. Hamer Clare, Mark Wellard R., Pell Gaby, Phillips Lisa, Nelson Barnaby, Paul Amminger G., R. Yung Alison, Jackson Graeme, Velakoulis Dennis, Pantelis Christos, Manji Husseini and D McGorry Patrick, Neuroprotective Effects of Low-dose Lithium in Individuals at Ultra-high Risk for Psychosis. A Longitudinal MRI/MRS Study, Current Pharmaceutical Design 2012; 18 (4) . https://dx.doi.org/10.2174/138161212799316163