Open Access
and Olanzapine Treatment on Prefrontal Cortical Function in Patients With Schizophrenia
Alessandro Bertolino,Giuseppe Blasi,Mariapia De Candia,Vittoria Petruzzella,Mario Altamura,Gaetano Nappi,Sergio Papa,Joseph H. Callicott,Venkata S. Mattay,Antonello Bellomo,Tommaso Scarabino,Daniel R. Weinberger,Marcello Nardini +12 more
- 01 Jan 2004
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TL;DR: Evaluated patients with schizophrenia with acute untreated schizophrenia suggest that a genetically determined variation in prefrontal dopamine catabolism impacts the therapeutic profile of olanzapine.
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Abstract: Objective: Deficits in working memory and in prefrontal cortical physiology are important outcome measures in schizophrenia, and both have been associated with dopamine dysregulation and with a functional polymorphism (Val 108/158 Met) in the catechol O-methyltransferase (COMT) gene that affects dopamine inactivation in the prefrontal cortex. The purpose of the present study was to evaluate in patients with schizophrenia the effect of COMT genotype on symptom variation, working memory performance, and prefrontal cortical physiology in response to treatment with an atypical antipsychotic drug. Method: Thirty patients with acute untreated schizophrenia were clinically evaluated with the Positive and Negative Syndrome Scale, underwent COMT Val/Met genotyping, and entered an 8-week prospective study of olanzapine treatment. Twenty patients completed two 3-T functional magnetic resonance imaging scans at 4 and 8 weeks during performance of N-back working memory tasks. Results: There was a significant interaction of COMT genotype and the effects of olanzapine on prefrontal cortical function. Met allele load predicted improvement in working memory performance and prefrontal physiology after 8 weeks of treatment. A similar effect was found also for negative symptoms assessed with the Positive and Negative Syndrome Scale. Conclusions: These results suggest that a genetically determined variation in prefrontal dopamine catabolism impacts the therapeutic profile of olanzapine.
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Genes, cognition and brain through a COMT lens.
Dwight Dickinson,Brita Elvevåg +1 more
TL;DR: The rapidly evolving literature exploring the association between COMT genotype and cognitive performance is reviewed, and it is illustrated how this polymorphism has served a pivotal role in characterizing various interacting dimensions of complexity in the relationship between genes and cognition.
242
Cognitive heterogeneity in schizophrenia.
TL;DR: Larger, better controlled studies are needed before the genetic sources of cognitive heterogeneity in schizophrenia can be accurately characterized, and this will be aided with the development and use of more specific neuropsychological tasks that can accurately discriminate between different cognitive domains.
193
Functional integration between the posterior hippocampus and prefrontal cortex is impaired in both first episode schizophrenia and the at risk mental state
Stefania Benetti,Andrea Mechelli,Marco Picchioni,Matthew R. Broome,Steven Williams,Philip McGuire +5 more
TL;DR: Perturbed hippocampal-prefrontal interactions are evident in individuals at high risk of developing psychosis and in patients who have just developed schizophrenia, which suggests that it may be a correlate of increased vulnerability to psychosis and that it is not attributable to an effect of chronic illness or its treatment.
Neuroimaging of cognitive disability in schizophrenia: search for a pathophysiological mechanism.
TL;DR: This article reviews how functional neuroimaging research of cognitive dysfunction in schizophrenia has resulted in a progression of influential pathophysiological models of the disorder, and how fMRI can help facilitate development of novel psychosocial and pharmacological interventions designed to improve cognition and functional outcome in patients with schizophrenia.
Functional and structural brain correlates of theory of mind and empathy deficits in schizophrenia
Francesco Benedetti,Alessandro Bernasconi,Marta Bosia,Roberto Cavallaro,Sara Dallaspezia,Andrea Falini,Sara Poletti,Daniele Radaelli,Roberta Riccaboni,Giuseppe Scotti,Enrico Smeraldi +10 more
TL;DR: Functional and structural abnormalities were observed in areas affected by the schizophrenic process early in the illness course, and known to be crucial for social cognition, suggesting a biological basis forSocial cognition deficits in schizophrenia.
164
References
Statistical parametric maps in functional imaging: A general linear approach
Karl J. Friston,Andrew P. Holmes,Keith J. Worsley,J-B. Poline,Chris D. Frith,Richard S. J. Frackowiak +5 more
TL;DR: In this paper, the authors present a general approach that accommodates most forms of experimental layout and ensuing analysis (designed experiments with fixed effects for factors, covariates and interaction of factors).
•Book
Co-planar stereotaxic atlas of the human brain : 3-dimensional proportional system : an approach to cerebral imaging
J. Talairach,Pierre Tournoux,Mark Rayport +2 more
- 01 Jan 1988
TL;DR: Direct and Indirect Radiologic Localization Reference System: Basal Brain Line CA-CP Cerebral Structures in Three-Dimensional Space Practical Examples for the Use of the Atlas in Neuroradiologic Examinations Three- Dimensional Atlas of a Human Brain Nomenclature-Abbreviations Anatomic Index Conclusions.
9.9K
Implications of normal brain development for the pathogenesis of schizophrenia
TL;DR: The findings suggest that nonspecific histopathology exists in the limbic system, diencephalon, and prefrontal cortex, that the pathology occurs early in development, and that the causative process is inactive long before the diagnosis is made.
3.8K
•Book
Human memory : theory and practice
Alan D. Baddeley
- 01 Jan 1990
TL;DR: This book discusses memory, Emotion and Cognition, and the role of Memory in Cognition - Working Memory, as well as Implicit Memory and Recollection.
3.4K
Effect of COMT Val108/158 Met genotype on frontal lobe function and risk for schizophrenia.
Michael F. Egan,Terry E. Goldberg,Bhaskar Kolachana,Joseph H. Callicott,C.M. Mazzanti,Richard E. Straub,David Goldman,Daniel R. Weinberger +7 more
TL;DR: The data suggest that the COMT Val allele, because it increases prefrontal dopamine catabolism, impairs prefrontal cognition and physiology, and by this mechanism slightly increases risk for schizophrenia.
2.6K
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