title: Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms.
abstract: First-generation antipsychotics have been associated with striatal volume increases. The effects of second-generation antipsychotics (SGAs) on the striatum are unclear. Moreover, SGAs may have neuroprotective effects on the hippocampus. Dose-dependent volumetric effects of individual SGAs have scarcely been investigated. Here we investigated structural brain changes in antipsychotic-naive, first-episode schizophrenia patients after 6 months treatment with the SGA, quetiapine. We have recently reported on baseline volume reductions in the caudate nucleus and hippocampus. Baseline and follow-up T1-weighted images (3 T) from 22 patients and 28 matched healthy controls were analysed using tensor-based morphometry. Non-parametric voxel-wise group comparisons were performed. Small volume correction was employed for striatum, hippocampus and ventricles. Dose-dependent medication effects and associations with psychopathology were assessed. Patients had significant bilateral striatal and hippocampal loss over the 6-month treatment period. When compared to controls the striatal volume loss was most pronounced with low quetiapine doses and less apparent with high doses. Post-hoc analyses revealed that the striatal volume loss was most pronounced in the caudate and putamen, but not in accumbens. Conversely, hippocampal volume loss appeared more pronounced with high quetiapine doses than with low doses. Clinically, higher baseline positive symptoms were associated with more striatal and hippocampal loss over time. Although patients' ventricles did not change significantly, ventricular increases correlated with less improvement of negative symptoms. Progressive regional volume loss in quetiapine-treated, first-episode schizophrenia patients may be dose-dependent and clinically relevant. The mechanisms underlying progressive brain changes, specific antipsychotic compounds and clinical symptoms warrant further research.
authors.affiliation: Centre for Neuropsychiatric Schizophrenia Research, CNSR, Psychiatric Centre Glostrup, Copenhagen University Hospital, Glostrup, Denmark. bebdrup@cnsr.dk
authors.forename: Bjørn H
authors.initials: BH
authors.lastname: Ebdrup
authors.forename: Arnold
authors.initials: A
authors.lastname: Skimminge
authors.forename: Hans
authors.initials: H
authors.lastname: Rasmussen
authors.forename: Bodil
authors.initials: B
authors.lastname: Aggernaes
authors.forename: Bob
authors.initials: B
authors.lastname: Oranje
authors.forename: Henrik
authors.initials: H
authors.lastname: Lublin
authors.forename: William
authors.initials: W
authors.lastname: Baaré
authors.forename: Birte
authors.initials: B
authors.lastname: Glenthøj
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D003987:Dibenzothiazepines / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014150:Antipsychotic Agents; D003987:Dibenzothiazepines; D000069348:Quetiapine Fumarate