title: The effect of clozapine on regional cerebral blood flow and brain metabolite ratios in schizophrenia: relationship with treatment response.
abstract: The purpose of this study was to investigate the effect of clozapine on regional cerebral blood flow (rCBF) and its relationship with response to treatment. In addition, we aimed to study the influence of clozapine on proton magnetic resonance spectroscopy ((1)H-MRS) findings in the dorsolateral prefrontal cortex (DLPFC) in a subgroup of patients. Psychopathology, neurocognitive functioning, and SPECT imaging of 22 patients were assessed at the baseline and 8 weeks after the initiation of clozapine treatment. In 10 of these patients intermediate-echo (TE: 135 ms) single-voxel (1)H-MRS was also performed at the baseline and after 8 weeks. Clozapine treatment increased the right frontal (superior and medial)/caudate perfusion ratio in the whole group, while it increased bilateral frontal (superior and medial)/caudate perfusion ratios in treatment responders. In addition, percentage changes in left and right frontal (superior and medial)/caudate perfusion ratios compared to the baseline were higher in treatment responders than in non-responders. The improvement in attention was related to the increase in percentage change in the right frontal (superior and medial)/caudate perfusion ratio, while the improvement in verbal fluency was related to the increase in percentage changes in both right and left frontal (superior and medial)/caudate perfusion ratios and to right frontal (superior and medial)/thalamus perfusion. Baseline frontal (superior and medial)/thalamus perfusion could explain 32% of the variability of percentage improvements in psychopathology. (1)H-MRS showed that the baseline PANSS general psychopathology score was inversely correlated with the baseline NAA/Cre ratio. An increased NAA/Cre ratio in DLPFC after 8 weeks of clozapine treatment was also revealed by (1)H-MRS. Our SPECT imaging results suggest the presence of an imbalance in fronto-striato-thalamic circuitry that changes with clozapine, especially in the responders, while (1)H-MRS results indicate a supportive effect of clozapine on neuronal integrity.
authors.affiliation: Hacettepe University, Faculty of Medicine, Department of Psychiatry, Ankara, Turkey. aertugru@hacettepe.edu.tr
authors.forename: Aygun
authors.initials: A
authors.lastname: Ertugrul
authors.forename: Bilge
authors.initials: B
authors.lastname: Volkan-Salanci
authors.forename: Koray
authors.initials: K
authors.lastname: Basar
authors.forename: Kader
authors.initials: K
authors.lastname: Karli Oguz
authors.forename: Basaran
authors.initials: B
authors.lastname: Demir
authors.forename: Eser Lay
authors.initials: EL
authors.lastname: Ergun
authors.forename: Senem
authors.initials: S
authors.lastname: Senturk
authors.forename: Belkis
authors.initials: B
authors.lastname: Erbas
authors.forename: Aysenur
authors.initials: A
authors.lastname: Cila
authors.forename: Berna
authors.initials: B
authors.lastname: Ulug
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001921:Brain / Q000098:blood supply / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000378:metabolism; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003024:Clozapine / Q000494:pharmacology* / Q000627:therapeutic use*; D004583:Electrons; D005260:Female; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D011569:Psychiatric Status Rating Scales; D012039:Regional Blood Flow / Q000187:drug effects*; D012559:Schizophrenia / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D003024:Clozapine