ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Progressive Brain Atrophy and Cortical Thinning in Schizophrenia after Commencing Clozapine Treatment.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers, 3 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
37 citing papers in PubMed, 3 syntheses or guidelines pooled it, 68 citations in OpenAlex.
- Molecular and topographic mapping of antipsychotic effects: a meta-analysis of postsynaptic density proteins in animal models with translational implications.Molecular psychiatry · 2026Pooled it
- Variation in fourteen brain structure volumes in schizophrenia: A comprehensive meta-analysis of 246 studies.Neuroscience and biobehavioral reviews · 2019Pooled it
- Brain-imaging studies of treatment-resistant schizophrenia: a systematic review.The lancet. Psychiatry · 2016Pooled it
- Brain Structure Measurements Predict Individualized Treatment Outcome of 12-Week Antipsychotic Monotherapies in First-episode Schizophrenia.Schizophrenia bulletin · 2023Trial
- Biodistribution, Tumor Detection, and Radiation Dosimetry ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2019Trial
- Cytokine and C-reactive protein concentrations over 6 months of treatment with clozapine in treatment resistant schizophrenia.Brain, behavior, & immunity - health · 2026Article
- Longitudinal brain structural changes during clozapine treatment: associations with neuroreceptor architecture and clinical response.medRxiv : the preprint server for health sciences · 2026Article
- Default Mode Network, Disorganization, and Treatment-Resistant Schizophrenia.Schizophrenia bulletin · 2026Article
- Neural substrates of treatment-resistant schizophrenia and the response to clozapine: A structural MRI study in a clinical setting.PloS one · 2026Article
- Machine learning-based morphological brain analysis in schizophrenia and unaffected siblings: a multisite study of potential risk markers.Frontiers in neuroscience · 2026Article
- Two structural alteration patterns of the thalamus in patients with schizophrenia.BMC medicine · 2025Article
- Molecular Underpinning of Treatment-Resistant Schizophrenia: A Putative Different Neurobiology from Treatment-Responsive Schizophrenia.International journal of molecular sciences · 2025Review
- Subcortical volumes, frontal cortical thickness, and pro-inflammatory cytokines in schizophrenia versus methamphetamine-induced psychosis.Brain imaging and behavior · 2025Article
- Disease Progression Patterns of Brain Morphology in Schizophrenia: More Progressed Stages in Treatment Resistance.Schizophrenia bulletin · 2024Article
- Neurostructural changes in schizophrenia and treatment-resistance: a narrative review.Psychoradiology · 2024Review
- A systematic review of neuroimaging studies of clozapine-resistant schizophrenia.Schizophrenia (Heidelberg, Germany) · 2023Review
- Investigating the symptomatic and morphological changes in the brain based on pre and post-treatment: A critical review from clinical to neuroimaging studies on schizophrenia.IBRO neuroscience reports · 2023Article
- Cortical thinning in relation to impaired insight into illness in patients with treatment resistant schizophrenia.Schizophrenia (Heidelberg, Germany) · 2023Article
- Resting-state functional MRI in treatment-resistant schizophrenia.Frontiers in neuroimaging · 2023Review
- Subcortical volume reduction and cortical thinning 3 months after switching to clozapine in treatment resistant schizophrenia.Schizophrenia (Heidelberg, Germany) · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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