title: Neuroprotective effects of low-dose lithium in individuals at ultra-high risk for psychosis. A longitudinal MRI/MRS study.
abstract: OBJECTIVE
  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.
authors.affiliation: ORYGEN Youth Health Research Centre, Locked Bag 10, Parkville, Victoria, 3052, Australia. gregor.berger@ipw.zh.ch
authors.forename: Gregor E
authors.initials: GE
authors.lastname: Berger
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Wood
authors.forename: Margaret
authors.initials: M
authors.lastname: Ross
authors.forename: Clare A
authors.initials: CA
authors.lastname: Hamer
authors.forename: R Mark
authors.initials: RM
authors.lastname: Wellard
authors.forename: Gaby
authors.initials: G
authors.lastname: Pell
authors.forename: Lisa
authors.initials: L
authors.lastname: Phillips
authors.forename: Barnaby
authors.initials: B
authors.lastname: Nelson
authors.forename: G Paul
authors.initials: GP
authors.lastname: Amminger
authors.forename: Alison R
authors.initials: AR
authors.lastname: Yung
authors.forename: Graeme
authors.initials: G
authors.lastname: Jackson
authors.forename: Dennis
authors.initials: D
authors.lastname: Velakoulis
authors.forename: Christos
authors.initials: C
authors.lastname: Pantelis
authors.forename: Husseini
authors.initials: H
authors.lastname: Manji
authors.forename: Patrick D
authors.initials: PD
authors.lastname: McGorry
mesh_terms: D000293:Adolescent; D000328:Adult; D005260:Female; D006801:Humans; D008094:Lithium / Q000008:administration & dosage*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010865:Pilot Projects; D011618:Psychotic Disorders / Q000175:diagnosis* / Q000188:drug therapy* / Q000523:psychology; D012307:Risk Factors; D055815:Young Adult
chemical_list: D018696:Neuroprotective Agents; D008094:Lithium