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Associations of SNAP-25 polymorphisms with cognitive dysfunctions in Caucasian patients with schizophrenia during a brief trail of treatment with atypical antipsychotics

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Abstract

The synaptosomal-associated protein of 25 kDa (SNAP-25) is part of the soluble N-ethylmaleimide-sensitive fusion protein (NSF) attachment receptor (SNARE), which mediates synaptic neurotransmission. In earlier studies a possible involvement of this protein in schizophrenia has been shown. As neurocognitive impairment is a core feature in the pathology of schizophrenia and considered to be a putative endophenotype according to genetic studies we investigated the influences of different SNAP-25 polymorphisms on neuropsychological test results before and during treatment with atypical antipsychotics. A total of 104 schizophrenic patients treated with atypical antipsychotics were genotyped for three different polymorphisms of the SNAP-25 gene (MnlI, TaiI and DdeI in the 3′-UTR). Cognitive function was assessed at baseline, week 4 or 6 and week 8 or 12. Results of individual neuropsychological tests were assigned to six cognitive domains (reaction time and quality; executive function; working, verbal and visual memory) and a general cognitive index. The MnlI and TaiI polymorphisms showed no associations to deficits on neuropsychological test results. In contrast, we observed a significant relation between the DdeI polymorphism of the SNAP-25 gene and cognitive dysfunctions. Homozygote T/T allele carriers of the DdeI polymorphism showed significant better neuropsychological test results in cognitive domains verbal memory and executive functions than those with the combined T/C and C/C genotypes (P < 0.01) at all three time points, but no differences in response to treatment with atypical antipsychotics. Additionally, TT carriers exhibited significantly better results in a general cognitive index (P < 0.05). As we observed an association between the DdeI polymorphism of the SNAP-25 gene and cognitive dysfunctions of schizophrenic patients our finding suggests that the SNAP-25 gene could play a role in the pathophysiology of neurocognitive dysfunctions in schizophrenia but is not predictive for treatment response with atypical antipsychotics.

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Acknowledgments

We thank the following persons for their excellent assistance: Judith Nuernberger, Nadine Schaaf, Ricarda Zimmermann, Markus Opgen-Rhein, Katja Maino, Rebecca Schennach, Larissa de la Fontaine, Mitja Jandl, Stefanie Behrens, Sylvia de Jonge, Karin Neumeier.

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  1. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University of Munich, Nußbaumstrasse 7, 80336, Munich, Germany

    Ilja Spellmann MD, Norbert Müller MD, Richard Musil MD, Peter Zill PhD, Anette Douhet MD, Sandra Dehning MD, Anja Cerovecki, Brigitta Bondy MD, Hans-Jürgen Möller MD & Michael Riedel MD

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  1. Ilja Spellmann MD
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  2. Norbert Müller MD
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Spellmann, I., Müller, N., Musil, R. et al. Associations of SNAP-25 polymorphisms with cognitive dysfunctions in Caucasian patients with schizophrenia during a brief trail of treatment with atypical antipsychotics. Eur Arch Psychiatry Clin Neurosc 258, 335–344 (2008). https://doi.org/10.1007/s00406-007-0800-9

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