The effect of clozapine on regional cerebral blood flow and brain metabolite ratios in schizophrenia: Relationship with treatment response

Ertuğrul, Aygün; Salancı, Bilge Volkan; Başar, Koray; Oğuz, Kader Karlı; Demir, Başaran; Ergün, Eser Lay; Şentürk, Senem; Erbaş, Belkıs; Cila, Ayşenur; Uluğ, Berna

doi:10.1016/j.pscychresns.2009.04.007

Cited by 63 publications

(69 citation statements)

References 52 publications

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“…No effects of chlorpromazine equivalents on capillary area density were found. These findings are in line with the results of in vivo studies demonstrating that while the atypical neuroleptic clozapine can improve negative symptoms and cognitive dysfunctions, it cannot improve reduced blood flow in the frontal lobes [29]. Both antipsychotics and antidepressants are known to increase proliferation of neuronal and endothelial cells in the hippocampus [30].…”

Section: Discussionsupporting

confidence: 85%

Reduced Capillary Density in the Prefrontal Cortex in Schizophrenia

Uranova¹,

Zimina²,

Vikhreva³

et al. 2013

AJMSM

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Neuroimaging studies have shown that the core symptoms of schizophrenia are associated with local changes of cerebral blood flow, particularly in the frontal cortex. Previously we reported ultrastructural damage of capillaries in the upper layers of the prefrontal cortex, Brodmann's area (BA) 10 and in the visual cortex, BA 17 in schizophrenia. An electron microscopic morphometric study was performed to estimate capillary area density (N cap/mm 2 ) in two upper layers of the prefrontal and visual cortices in 26 cases of schizophrenia and 26 normal controls. Capillary area density was lower in the prefrontal cortex in the schizophrenia group (-24%, p < 0.001) and in the subgroup of schizophrenia with predominantly negative symptoms (n=12, -35%, p < 0.001) as compared to controls. Group and subgroup differences were absent in the visual cortex. Dysfunction of neocortical microvasculature in schizophrenia is related to region-specific capillary deficiency in the prefrontal cortex. These changes might contribute to the lowered blood flow, reduced glucose metabolic rates, resting hypofrontality and hypoactivation reported in the prefrontal cortex of patients with schizophrenia.

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Section: Discussionsupporting

confidence: 85%

Reduced Capillary Density in the Prefrontal Cortex in Schizophrenia

Uranova¹,

Zimina²,

Vikhreva³

et al. 2013

AJMSM

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show abstract

“…One functional magnetic resonance imaging (fMRI) study has reported a correlation between improved insight and activation of the left medial prefrontal cortex after recovering from an acute episode. 27 Technetium-99m ethyl cysteinate dimer single photon emission computed tomography (99mTc ECD-SPECT) is a valuable functional brain imaging tool to study regional cerebral blood flow (rCBF) in patients with a variety of psychiatric disorders, 23 including schizophrenia. [25][26][27][28] In this study, we investigated the functional substrate underlying preserved insight in patients with schizophrenia in comparison with those with impaired insight and psychiatrically healthy controls using whole-brain 99mTc ECD-SPECT voxel-based statistical analysis of rCBF.…”

Section: Introductionmentioning

confidence: 99%

Schizophrenia with preserved insight is associated with increased perfusion of the precuneus

Faget-Agius

Boyer

Padovani

et al. 2012

J Psychiatry Neurosci

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“…23,47 The absence of significant differences in NAA levels 25 22 patients CLZ Previous typical and atypical AP Neuroimaging of clozapine across the groups evaluated in the studies may suggest a normalization of this marker with the use of clozapine. 24 Previous use of typical antipsychotics should also be considered as a possible explanation, since this class of antipsychotics has been associated with lower NAA levels in the thalamus and frontal lobe of patients compared to controls.…”

Section: Discussionmentioning

confidence: 89%

“…31 Conversely, one study found significantly increased perfusion in regions of the frontal lobe comparing patients without medication and the same group of patients 8 weeks after the initiation of clozapine treatment. 25 Clozapine treatment was also associated with increased cerebral blood flow (CBF) in the dorsolateral prefrontal cortex and reduced CBF in the ventrolateral frontal cortex in comparison with haloperidol treatment and untreated controls. 33 A pattern of decreased activation in the region of the basal ganglia in association with the use of clozapine was found in four studies.…”

Section: Positron Emission Tomography (Pet) and Single-photon Emissiomentioning

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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The effect of clozapine on regional cerebral blood flow and brain metabolite ratios in schizophrenia: Relationship with treatment response

Cited by 63 publications

References 52 publications

Reduced Capillary Density in the Prefrontal Cortex in Schizophrenia

Reduced Capillary Density in the Prefrontal Cortex in Schizophrenia

Schizophrenia with preserved insight is associated with increased perfusion of the precuneus

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

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