Abstract
In light of current etiological concepts the glutamatergic system plays an essential role for the pathophysiology of the disorder, offering multiple options for new treatment strategies. The D-amino oxidase activator (DAOA) gene is closely connected to the glutamatergic system and its therapeutic and pathophysiological relevance for schizophrenia is therefore intensively debated. In a further step to shed light on the role of DAOA in schizophrenia, we aimed to investigate the association of the functional DAOA Arg30Lys (rs2391191) variant and cortical thickness in schizophrenia. Cortical thickness was computed by an automated surface-based technique (FreeSurfer) in 52 genotyped patients with schizophrenia and 42 healthy controls. Cortical thickness of the entire cortex was compared between risk carriers and non-risk carriers regarding the Arg30Lys polymorphism in patients and healthy controls on the basis of a node-by-node procedure and an automated clustering approach. Risk carriers with schizophrenia show significantly thinner cortex in two almost inversely arranged clusters on the left and right hemisphere comprising middle temporal, inferior parietal, and lateral occipital cortical areas. The clusters encompass an area of 1174 mm2 (left) and 1156 mm2 (right). No significant effect was observed in healthy controls.
The finding of our study that the Arg30Lys risk variant is associated with a distinct cortical thinning provides new evidence for the pathophysiological impact of DAOA in schizophrenia. The affected areas are mostly confined to cortical regions with a crucial role in the ToM network and visual processing, which both can be influenced by glutamatergic modulation. Our finding thus underlines the importance of DAOA and related glutamatergic processes as a putative target for therapeutic interventions in schizophrenia.
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Acknowledgements
This work was supported by the Bundesministerium für Bildung und Forschung, BMBF Grant 01GW0740 and the Interdisciplinary Center for Clinical Research of the University of Jena (IZKF). The sponsor served no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the paper for publication.
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The authors declare that HS received compensation from Otsuka and Lilly in 2008. All of the authors reported no financial, personal, or other relationships with other people or organizations that could inappropriately influence, or be perceived to influence, their work.
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Schultz, C., Nenadic, I., Koch, K. et al. Reduced Cortical Thickness is Associated with the Glutamatergic Regulatory Gene Risk Variant DAOA Arg30Lys in Schizophrenia. Neuropsychopharmacol 36, 1747–1753 (2011). https://doi.org/10.1038/npp.2011.56
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DOI: https://doi.org/10.1038/npp.2011.56
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