Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms

Bjørn H Ebdrup; Arnold Skimminge; Hans Rasmussen; Bodil Aggernaes; Bob Oranje; Henrik Lublin; William Baaré; Birte Glenthøj

doi:10.1017/s1461145710000817

Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms

Bjørn H Ebdrup, Arnold Skimminge, Hans Rasmussen, Bodil Aggernaes, Bob Oranje, Henrik Lublin, William Baaré, Birte Glenthøj

60 Citations (Scopus)

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.

Original language	English
Journal	International Journal of Neuropsychopharmacology
Volume	14
Pages (from-to)	69-82
Number of pages	14
ISSN	1461-1457
DOIs	https://doi.org/10.1017/s1461145710000817
Publication status	Published - Feb 2011

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Ebdrup, B. H., Skimminge, A., Rasmussen, H., Aggernaes, B., Oranje, B., Lublin, H., Baaré, W., & Glenthøj, B. (2011). Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. International Journal of Neuropsychopharmacology, 14, 69-82. https://doi.org/10.1017/s1461145710000817

Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms. / Ebdrup, Bjørn H; Skimminge, Arnold; Rasmussen, Hans et al.

In: International Journal of Neuropsychopharmacology, Vol. 14, 02.2011, p. 69-82.

Research output: Contribution to journal › Journal article › Research › peer-review

Ebdrup, BH, Skimminge, A, Rasmussen, H, Aggernaes, B, Oranje, B, Lublin, H, Baaré, W & Glenthøj, B 2011, 'Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms', International Journal of Neuropsychopharmacology, vol. 14, pp. 69-82. https://doi.org/10.1017/s1461145710000817

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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.",

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AB - 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.

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ER -

Progressive striatal and hippocampal volume loss in initially antipsychotic-naive, first-episode schizophrenia patients treated with quetiapine: relationship to dose and symptoms

Abstract

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