The Effect of Clozapine on Caudate Nucleus Volume in Schizophrenic Patients Previously Treated with Typical Antipsychotics

Scheepers, Floortje

doi:10.1016/s0893-133x(00)00172-x

Cited by 120 publications

(80 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Seven longitudinal studies using an ROI approach focused on basal ganglia [40][41][42][43][44][45][46], one on the thalamus [47], one on the anterior cingulate gyrus [48] and two studies on other cortical regions [25,49]. Five studies evaluated GM changes after treatment with atypical antipsychotic medication only [25,40,43,45,47], four compared typical versus atypical antipsychotic [41,44,46,48] and two did not examine for the differences between these two subtypes of antipsychotic drugs [42,49].…”

Section: Longitudinal Studies Using a Region-of-interest (Roi) Approachmentioning

confidence: 99%

“…In the group of risperidone-treated patients, who later switched to olanzapine, no significant differences in overall basal ganglia volume were seen [44]. Treatment with clozapine in schizophrenic patients previously treated with typical antipsychotics resulted in decreased caudate volume [45]. Volume of caudate and nucleus lentiformis increased after exposure to typical antipsychotics and decreased following exposure to atypical antipsychotics [46].…”

Section: Longitudinal Studies Using a Region-of-interest (Roi) Approachmentioning

confidence: 99%

See 1 more Smart Citation

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

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.

show abstract

Section: Longitudinal Studies Using a Region-of-interest (Roi) Approachmentioning

confidence: 99%

Section: Longitudinal Studies Using a Region-of-interest (Roi) Approachmentioning

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

show abstract

“…For example, typical antipsychotic agents have consistently but not universally been associated with increased volume of the basal ganglia including the caudate (Scherk and Falkai, 2006;Ebdrup et al, 2013). However, clozapine monotherapy has consistently been associated with a reduction in caudate volume (Scheepers et al, 2001;van Haren et al, 2007), with this reduction in volume associated with clinical improvement (Scheepers et al, 2001). Similarly, in contrast to typical antipsychotic agents (Lieberman et al, 2005;van Haren et al, 2007), clozapine treatment has been associated in longitudinal studies with either an increase (Molina et al, 2005) or an attenuated loss of volume of the frontal lobe compared with typical antipsychotic agents (van Haren et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment

Ahmed

Cannon

Scanlon

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Despite evidence that clozapine may be neuroprotective, there are few longitudinal magnetic resonance imaging (MRI) studies that have specifically explored an association between commencement of clozapine treatment for schizophrenia and changes in regional brain volume or cortical thickness. A total of 33 patients with treatment-resistant schizophrenia and 31 healthy controls matched for age and gender underwent structural MRI brain scans at baseline and 6-9 months after commencing clozapine. MRI images were analyzed using SIENA (Structural Image Evaluation, using Normalization, of Atrophy) and FreeSurfer to investigate changes over time in brain volume and cortical thickness respectively. Significantly greater reductions in volume were detected in the right and left medial prefrontal cortex and in the periventricular area in the patient group regardless of treatment response. Widespread further cortical thinning was observed in patients compared with healthy controls. The majority of patients improved symptomatically and functionally over the study period, and patients who improved were more likely to have less cortical thinning of the left medial frontal cortex and the right middle temporal cortex. These findings demonstrate on-going reductions in brain volume and progressive cortical thinning in patients with schizophrenia who are switched to clozapine treatment. It is possible that this gray matter loss reflects a progressive disease process irrespective of medication use or that it is contributed to by switching to clozapine treatment. The clinical improvement of most patients indicates that antipsychotic-related gray matter volume loss may not necessarily be harmful or reflect neurotoxicity.

show abstract

“…21 MRI studies in humans have also suggested a possible effect of dopamine function on morphometric measures, as treatment with typical antipsychotics such as haloperidol may increase the volume of the caudate nucleus. [22][23][24][25] Even in more intermediate phenotypes, single gene effects are likely to be small, introducing a significant risk of false-positive findings. Of additional value then is the approach of constraining investigations by including prior knowledge of the genes of interest, such as their pattern and timing of expression.…”

mentioning

confidence: 99%

Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls

et al. 2005

View full text Add to dashboard Cite

Genetic influences on behavior are complex and, as such, the effect of any single gene is likely to be modest. Neuroimaging measures may serve as a biological intermediate phenotype to investigate the effect of genes on human behavior. In particular, it is possible to constrain investigations by prior knowledge of gene characteristics and by including samples of subjects where the distribution of phenotypic variance is both wide and under heritable influences. Here, we use this approach to show a dissociation between the effects of two dopamine genes that are differentially expressed in the brain. We show that the DAT1 gene, a gene expressed predominantly in the basal ganglia, preferentially influences caudate volume, whereas the DRD4 gene, a gene expressed predominantly in the prefrontal cortex, preferentially influences prefrontal gray matter volume in a sample of subjects including subjects with ADHD, their unaffected siblings, and healthy controls. This demonstrates that, by constraining our investigations by prior knowledge of gene expression, including samples in which the distribution of phenotypic variance is wide and under heritable influences, and by using intermediate phenotypes, such as neuroimaging, we may begin to map out the pathways by which genes influence behavior. Investigators interested in the effect of genes on behavior face a challenge in that behavior is complex, and is likely affected by multiple genes, as well as gene-gene and gene-environment interactions. As such, the effect of any single gene on behavior is probably only small. Indeed, studies investigating the effect of genotype on behavior have reported modest associations. For example, Fossella et al 1 described the influence of four genes related to dopamine function on measures of executive attention and report small effect sizes. Furthermore, their effects were subtle in that not all aspects of executive attention were affected and that genes had differential effects. 1

show abstract

The Effect of Clozapine on Caudate Nucleus Volume in Schizophrenic Patients Previously Treated with Typical Antipsychotics

Cited by 120 publications

References 76 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

Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment

Differential effects of DRD4 and DAT1 genotype on fronto-striatal gray matter volumes in a sample of subjects with attention deficit hyperactivity disorder, their unaffected siblings, and controls

Contact Info

Product

Resources

About