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CACNA1C genotype explains interindividual differences in amygdala volume among patients with schizophrenia

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Abstract

Affective deficits are one common denominator of schizophrenia (SZ), bipolar disorder (BD) and obsessive compulsive disorder (OCD) with the amygdala indicated as one of the major structures involved in emotion regulation. Previous findings of differences in amygdala volume between healthy controls and patients with SZ, BD or OCD diverge with respect to the affected hemisphere, size and direction of the effect. Variability in the CACNA1C gene has been linked to BD, SZ as well as structural and functional variation in the amygdala in healthy people and patients with BD. We were interested to investigate whether amygdala volumes differ between hemispheres, diagnostic or genotype groups, and whether any interactive effects exist. We combined genotyping of SNP rs1006737 in CACNA1C with structural MRI measurements of relative gray matter (GM) amygdala volume in patients with SZ, BD or OCD as well as healthy controls (N Total = 72). The CACNA1C genotype showed a significant effect on relative GM amygdala volume in patients with SZ. There was a significant left versus right relative GM amygdala volume decrease in patients with SZ or BD. The effects of hemisphere and diagnosis (controls vs. patients with SZ) on relative GM amygdala volume were genotype specific. Our data suggest that the CACNA1C genotype may account for some heterogeneity in the effects of hemisphere and diagnosis on amygdala volume when comparing patients with SZ and controls and point to disturbed Ca2+-signaling as a plausible mechanism contributing to the pathology in patients with SZ.

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Acknowledgments

We thank Patrick Menzel for assistance with the MRI data processing. This work was supported by a grant from the Competence Network Schizophrenia and partially supported by the Deutsche Forschungsgemeinschaft (DFG) via the Clinical Research Group 241 “Genotype-phenotype relationships and neurobiology of the longitudinal course of psychosis” (http://www.kfo241.de; Grant Number GR 1950/5-1) to OG.

Conflict of interest

CW, HM, TSA, AR, HS, AS and PF declare no biomedical financial interest or potential conflicts of interest. TW is a member of a speaker bureau for Alpine Biomed, AstraZeneca, Bristol-Meyers-Squibb, Eli Lilly, Jansen Cilag and Sanofi-Synthelabo and has received a research grant from AstraZeneca, I3G and AOK (health insurance company). OG was honorary speaker for the following companies: AstraZeneca, Bristol-Meyers-Squibb, Jansen Cilag, Lilly and Otsuka, has been invited to scientific congresses by AstraZeneca, Jansen Cilag, Pfizer and has received a research grant from Servier.

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Authors and Affiliations

  1. Department of Psychiatry and Psychotherapy, Center for Translational Research in Systems Neuroscience and Psychiatry, Georg-August-University Göttingen, Von-Siebold-Str. 5, 37075, Göttingen, Germany

    Claudia Wolf, Holger Mohr, Thomas Schneider-Axmann, Thomas Wobrock & Oliver Gruber

  2. Department of General Psychology, Technical University Dresden, Dresden, Germany

    Holger Mohr

  3. Department of Psychiatry and Psychotherapy, Ludwig Maximilians University, Munich, Germany

    Thomas Schneider-Axmann, Andrea Schmitt & Peter Falkai

  4. Department of Psychiatry and Psychotherapy, University of the Saarland, Saarbrücken, Germany

    Susanne Kraft

  5. Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany

    Andreas Reif

  6. AMEOS Clinic Osnabrück, Osnabrück, Germany

    Harald Scherk

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  1. Claudia Wolf
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Correspondence to Claudia Wolf.

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Wolf, C., Mohr, H., Schneider-Axmann, T. et al. CACNA1C genotype explains interindividual differences in amygdala volume among patients with schizophrenia. Eur Arch Psychiatry Clin Neurosci 264, 93–102 (2014). https://doi.org/10.1007/s00406-013-0427-y

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