Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia

Molina, Vicente; Reig, Santiago; Sanz, Javier; Palomo, Tomás; Benito, Carlos; Sánchez, J.; Sarramea, Fernando; Pascau, Javier; Desco, Manuel

doi:10.1016/j.schres.2005.07.031

Cited by 103 publications

(108 citation statements)

References 41 publications

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“…According to their clinical stage, patients with schizophrenia were considered as patients with a first episode (defined as first hospitalization [22], less than five years` total duration of disease [23]), recent onset (first hospitalization within the last 5 years [22]), chronic patients (disease duration greater than five years [24], disease duration more than ten years [23]), or therapy resistant chronic patients (chronic and refractory to conventional treatment [25]). We used the term antipsychotic-naïve for those patients who have never used any antipsychotic medication and 'antipsychotic-free' for patients free of antipsychotic medication for at least two months before admission [26].…”

Section: Selection Criteriamentioning

confidence: 99%

The Effects of Antipsychotics on the Brain: What Have We Learnt from Structural Imaging of Schizophrenia? – A Systematic Review

Smieskova

Fusar‐Poli²,

Allen³

et al. 2009

CPD

186

131

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Abstract:Despite a large number of neuroimaging studies in schizophrenia reporting subtle brain abnormalities, we do not know to what extent such abnormalities reflect the effects of antipsychotic treatment on brain structure. We therefore systematically reviewed cross-sectional and follow-up structural brain imaging studies of patients with schizophrenia treated with antipsychotics. 30 magnetic resonance imaging (MRI) studies were identified, 24 of them being longitudinal and six cross-sectional structural imaging studies. In patients with schizophrenia treated with antipsychotics, reduced gray matter volume was described, particularly in the frontal and temporal lobes. Structural neuroimaging studies indicate that treatment with typical as well as atypical antipsychotics may affect regional gray matter (GM) volume. In particular, typical antipsychotics led to increased gray matter volume of the basal ganglia, while atypical antipsychotics reversed this effect after switching. Atypical antipsychotics, however, seem to have no effect on basal ganglia structure.

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Section: Selection Criteriamentioning

confidence: 99%

The Effects of Antipsychotics on the Brain: What Have We Learnt from Structural Imaging of Schizophrenia? – A Systematic Review

Smieskova

Fusar‐Poli²,

Allen³

et al. 2009

CPD

186

131

View full text Add to dashboard Cite

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“…29,30 MRI studies using diffusion tensor imaging in vivo have indicated abnormalities in white matter in prefrontal cortex and other brain areas of patients with schizophrenia, indicating the possibility of disturbed maintenance of myelination through oligodendrocytes [31][32][33][34] although not all studies agree. 35,36 Recently, postmortem gene expression profiling has boosted the field by showing that many myelinrelated genes are downregulated in several brain regions of patients with schizophrenia compared with controls [37][38][39][40][41] Furthermore, it is interesting to note that while most of the myelination occurs shortly postnatally, 42 the peak of myelination in the cortical areas and especially in the prefrontal cortex occurs during the adolescence and early adulthood, 43,44 thus coinciding with a critical period for the onset of schizophrenia. 45,46 Myelin is composed of 70% cholesterol, and impaired cholesterol biosynthesis by disruption of the squalene synthase (an SREBP-controlled gene), has been shown to severely disrupt myelination.…”

Section: Abnormalities In Myelination and Lipid Biosynthesis In Schizmentioning

confidence: 99%

Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples

et al. 2008

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Several studies have reported structural brain abnormalities, decreased myelination and oligodendrocyte dysfunction in schizophrenia. In the central nervous system, glia-derived de novo synthesized cholesterol is essential for both myelination and synaptogenesis. Previously, we demonstrated in glial cell lines that antipsychotic drugs induce the expression of genes involved in cholesterol and fatty acids biosynthesis through activation of the sterol regulatory element binding protein (SREBP) transcription factors, encoded by the sterol regulatory element binding transcription factor 1 (SREBF1) and sterol regulatory element binding transcription factor 2 (SREBF2) genes. Considering the importance of these factors in the lipid biosynthesis and their possible involvement in antipsychotic drug effects, we hypothesized that genetic variants of SREBF1 and/or SREBF2 could affect schizophrenia susceptibility. We therefore conducted a HapMap-based association study in a large German sample, and identified association between schizophrenia and five markers in SREBF1 and five markers in SREBF2. Follow-up studies in two independent samples of Danish and Norwegian origin (part of the Scandinavian collaboration of psychiatric etiology study, SCOPE) replicated the association for the five SREBF1 markers and for two markers in SREBF2. A combined analysis of all samples resulted in highly significant genotypic P-values of 9 Â 10 À4 for SREBF1 (rs11868035, odd ration (OR) = 1.26, 95% confidence interval (CI) (1.09-1.45)) and 4 Â 10 À5 for SREBF2 (rs1057217, OR = 1.39, 95% CI (1.19-1.63)). This finding strengthens the hypothesis that SREBP-controlled cholesterol biosynthesis is involved in the etiology of schizophrenia.

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“…Regarding white and gray matter volume, Molina et al 18 found increased gray matter volume and reduced white matter volume after comparing a group on clozapine treatment and a healthy control group, with changes observed in total, frontal, parietal, and occipital volumes in comparison with controls. 18 Van Haren et al 19 investigated white and gray matter density in a longitudinal study and reported that the dose of clozapine accumulated per year during the 5-year follow-up study was related to a smaller reduction in density in the region of the left superior frontal gyrus compared with typical antipsychotic therapy. In a study comparing patients on clozapine and olanzapine, another atypical antipsychotic, Mattai et al 20 assessed gray matter cortical thickness and found the use of clozapine to be associated with thickness reduction in an area of the right prefrontal cortex.…”

Section: Structural Studiesmentioning

confidence: 99%

Structural and functional neuroimaging findings associated with the use of clozapine in schizophrenia: a systematic review

Garcia

Chagas

Silva

et al. 2015

Rev. Bras. Psiquiatr.

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Objective: Schizophrenia is one of the most severe psychiatric disorders, and its current treatment relies on antipsychotic medications with only partial effectiveness. Clozapine is an atypical antipsychotic with a specific profile of action indicated for treatment-resistant schizophrenia. Neuroimaging studies assessing the effects of clozapine could help shed light on the neural underpinnings of the effects of this drug in the brain. The objective of this study was to review the available literature on the structural and functional neuroimaging findings associated with use of clozapine. Method: We conducted a systematic review of the indexed literature using the PubMed, BIREME, and ISI Web of Knowledge search engines and the following keywords: clozapine, neuroimaging, computed tomography, MRI, functional magnetic resonance, PET, SPECT, and DTI. Results: A total of 23 articles were included in the review. In structural studies, the use of clozapine was associated with volume reductions in the basal ganglia, especially the caudate nucleus, where functional neuroimaging studies also found decreased perfusion. In the frontal lobe, clozapine treatment was associated with increased gray matter volume and reduced perfusion. Conclusion:The results of the studies reviewed suggest that the use of clozapine is associated with distinctive structural and functional neuroimaging findings that are not shared with other antipsychotics.

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Increase in gray matter and decrease in white matter volumes in the cortex during treatment with atypical neuroleptics in schizophrenia

Cited by 103 publications

References 41 publications

The Effects of Antipsychotics on the Brain: What Have We Learnt from Structural Imaging of Schizophrenia? – A Systematic Review

The Effects of Antipsychotics on the Brain: What Have We Learnt from Structural Imaging of Schizophrenia? – A Systematic Review

Polymorphisms in SREBF1 and SREBF2, two antipsychotic-activated transcription factors controlling cellular lipogenesis, are associated with schizophrenia in German and Scandinavian samples

Structural and functional neuroimaging findings associated with the use of clozapine in schizophrenia: a systematic review

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