title: Neuroprotection after a first episode of mania: a randomized controlled maintenance trial comparing the effects of lithium and quetiapine on grey and white matter volume.
abstract: Lithium and quetiapine are effective treatments for bipolar disorder, but their potential neuroprotective effects in humans remain unclear. A single blinded equivalence randomized controlled maintenance trial was conducted in a prospective cohort of first-episode mania (FEM) patients (n=26) to longitudinally compare the putative protective effects of lithium and quetapine on grey and white matter volume. A healthy control sample was also collected (n=20). Using structural MRI scans, voxel-wise grey and white matter volumes at baseline and changes over time in response to treatment were investigated. Patients were assessed at three time points (baseline, 3 and 12-month follow-up), whereas healthy controls were assessed at two time points (baseline and 12-month follow-up). Patients were randomized to lithium (serum level 0.6 mmol l-1, n=20) or quetiapine (flexibly dosed up to 800 mg per day, n=19) monotherapy. At baseline, compared with healthy control subjects, patients with FEM showed reduced grey matter in the orbitofrontal cortex, anterior cingulate, inferior frontal gyrus and cerebellum. In addition, patients had reduced internal capsule white matter volume bilaterally (t1,66>3.20, P<0.01). Longitudinally, there was a significant treatment × time effect only in the white matter of the left internal capsule (F2,112=8.54, P<0.01). Post hoc testing showed that, compared with baseline, lithium was more effective than quetiapine in slowing the progression of white matter volume reduction after 12 months (t1,24=3.76, P<0.01). Our data support the role of lithium but not quetiapine therapy in limiting white matter reduction early in the illness course after FEM.
authors.affiliation: IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, VIC, Australia.|Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.|Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia.|Orygen Youth Health Clinical Program, Parkville, VIC, Australia.|Barwon Health and the Geelong Clinic, Swanston Centre, Geelong, VIC, Australia.|Florey Institute for Neuroscience and Mental Health, Kenneth Myer Building, Royal Parade, Parkville, VIC, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Berk
authors.affiliation: Brain and Mental Health Laboratory, School of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, VIC, Australia.|Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.
authors.forename: O
authors.initials: O
authors.lastname: Dandash
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.|Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Daglas
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.|Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: S M
authors.initials: SM
authors.lastname: Cotton
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.|Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: K
authors.initials: K
authors.lastname: Allott
authors.affiliation: Brain and Mental Health Laboratory, School of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, VIC, Australia.
authors.forename: A
authors.initials: A
authors.lastname: Fornito
authors.affiliation: Brain and Mental Health Laboratory, School of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, VIC, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Suo
authors.affiliation: Brain and Mental Health Laboratory, School of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, VIC, Australia.|Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.
authors.forename: P
authors.initials: P
authors.lastname: Klauser
authors.affiliation: Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.|Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), and Division of Psychiatry, Karolinska Institutet, Stockholm, Sweden.
authors.forename: B
authors.initials: B
authors.lastname: Liberg
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.|Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: L
authors.initials: L
authors.lastname: Henry
authors.affiliation: Orygen Youth Health Clinical Program, Parkville, VIC, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Macneil
authors.affiliation: Orygen Youth Health Clinical Program, Parkville, VIC, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Hasty
authors.affiliation: Orygen, The National Centre of Excellence in Youth Mental Health, Parkville, VIC, Australia.|Centre for Youth Mental Health, University of Melbourne, Parkville, VIC, Australia.
authors.forename: P
authors.initials: P
authors.lastname: McGorry
authors.affiliation: Florey Institute for Neuroscience and Mental Health, Kenneth Myer Building, Royal Parade, Parkville, VIC, Australia.|Department of Psychiatry, Melbourne Neuropsychiatry Centre, University of Melbourne and Melbourne Health, Carlton South, VIC, Australia.
authors.forename: C
authors.initials: C
authors.lastname: Pantelis
authors.affiliation: Brain and Mental Health Laboratory, School of Psychological Sciences, Monash Institute of Cognitive and Clinical Neurosciences, Monash University, Clayton, VIC, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Yücel
mesh_terms: D018692:Antimanic Agents / Q000627:therapeutic use*; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005260:Female; D066128:Gray Matter / Q000000981:diagnostic imaging* / Q000473:pathology; D006801:Humans; D018020:Lithium Compounds / Q000627:therapeutic use*; D060046:Maintenance Chemotherapy; D008297:Male; D018696:Neuroprotective Agents; D009929:Organ Size; D000069348:Quetiapine Fumarate / Q000627:therapeutic use*; D016037:Single-Blind Method; D066127:White Matter / Q000000981:diagnostic imaging* / Q000473:pathology; D055815:Young Adult
chemical_list: D018692:Antimanic Agents; D014150:Antipsychotic Agents; D018020:Lithium Compounds; D018696:Neuroprotective Agents; D000069348:Quetiapine Fumarate