Anatomical and functional brain variables associated with clozapine response in treatment-resistant schizophrenia.
Clozapine alleviates the symptoms of a significant proportion of treatment-resistant schizophrenic patients. Previous studies suggest that the response to clozapine may be associated with prefrontal and temporal anatomy as well as with prefrontal, basal ganglia and thalamic metabolism. A sample of 25 treatment-resistant (TR) schizophrenic patients underwent magnetic resonance imaging (MRI) and 18F-deoxyglucose positron emission tomography (PET) before and after treatment with clozapine. We investigated the association between changes in positive, disorganized, and negative schizophrenic syndromes with clozapine treatment and a set of cerebral variables that included total intracranial volume (ICV); hippocampal, dorsolateral prefrontal (DLPF) and temporal gray-matter volume and metabolism; and metabolic activity of the thalamus, pallidum/putamen, and caudate head. Improvement in positive symptoms with clozapine was directly related to temporal gray-matter volume, whereas improvement of disorganization symptoms was inversely related to ICV and hippocampal volume. Patients with high baseline DLPF cortical volume and metabolic activity were more likely to experience improvement in their negative symptoms. We conclude that clinical improvement with clozapine may be related with the anatomy and metabolic activity of specific brain areas, with the structural integrity of the DLPF and temporal regions showing the maximum predictive capacity.
Molina
Vicente
V
Department of Psychiatry, Hospital Doce de Octubre, Edificio de Medicina Comunitaria, Avda de Córdoba, km 5.4, 28041 Madrid, Spain. vmolina@eresmas.net
Reig
Santiago
S
Sarramea
Fernando
F
Sanz
Javier
J
Francisco Artaloytia
Juan
J
Luque
Rogelio
R
Aragüés
María
M
Pascau
Javier
J
Benito
Carlos
C
Palomo
Tomás
T
Desco
Manuel
M
D000328:Adult; D014150:Antipsychotic Agents / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D001921:Brain / Q000033:anatomy & histology* / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use*; D004351:Drug Resistance; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000033:anatomy & histology / Q000187:drug effects; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D017397:Prefrontal Cortex / Q000033:anatomy & histology / Q000187:drug effects; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy*; D013702:Temporal Lobe / Q000033:anatomy & histology / Q000187:drug effects; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism; D014055:Tomography, Emission-Computed
D014150:Antipsychotic Agents; D003024:Clozapine