Abstract
We combined functional imaging and genetics to investigate the behavioral and neural effects of a dysbindin-1 (DTNBP1) genotype associated with the expression level of this important synaptic protein, which has been implicated in schizophrenia. On a working memory (WM) task for emotional faces, participants with the genotype related to increased expression showed higher WM capacity for happy faces compared with the genotype related to lower expression. Activity in several task-related brain areas with known DTNBP1 expression was increased, including hippocampal, temporal and frontal cortex. Although these increases occurred across emotions, they were mostly observed in areas whose activity correlated with performance for happy faces. This suggests effects of variability in DTNBP1 on emotion-specific WM capacity and region-specific task-related brain activation in humans. Synaptic effects of DTNBP1 implicate that altered dopaminergic and/or glutamatergic neurotransmission may be related to the increased WM capacity. The combination of imaging and genetics thus allows us to bridge the gap between the cellular/molecular and systems/behavioral level and extend the cognitive neuroscience approach to a comprehensive biology of cognition.
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Acknowledgements
This work was supported by the Wellcome Trust, Grant no. 077185/05Z, the Wales Institute of Cognitive Neuroscience (WICN) and the North West Wales NHS Trust. We thank Tony Bedson and the radiography team at Ysbyty Gwynedd, Bangor for the acquisition of the imaging data, Tony Bedson and Stefanie Linden for taking of blood samples, Robert Walters, head of laboratory services at Ysbyty Gwynedd, for help with the blood sample logistics, Chris Whitaker for expert advice on statistics, John Parkinson for helpful comments on the paper and all our participants.
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Wolf, C., Jackson, M., Kissling, C. et al. Dysbindin-1 genotype effects on emotional working memory. Mol Psychiatry 16, 145–155 (2011). https://doi.org/10.1038/mp.2009.129
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DOI: https://doi.org/10.1038/mp.2009.129
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