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A common risk variant in CACNA1C supports a sex-dependent effect on longitudinal functioning and functional recovery from episodes of schizophrenia-spectrum but not bipolar disorder

Heilbronner, Urs and Malzahn, Dörthe and Strohmaier, Jana and Maier, Sandra and Frank, Josef and Treutlein, Jens and Muhleisen, Thomas W. and Forstner, Andreas J. and Witt, Stephanie H. and Cichon, Sven and Falkai, Peter and Nothen, Markus M. and Rietschel, Marcella and Schulze, Thomas G.. (2015) A common risk variant in CACNA1C supports a sex-dependent effect on longitudinal functioning and functional recovery from episodes of schizophrenia-spectrum but not bipolar disorder. European Neuropsychopharmacology, 25 (12). pp. 2262-2270.

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Official URL: https://edoc.unibas.ch/61551/

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Abstract

Sex is a powerful modulator of disease susceptibility, course and outcome. The gene CACNA1C is among the best replicated vulnerability genes of bipolar disorder and schizophrenia. The aim of the present study was to investigate whether sex and a variant in CACNA1C (rs10774035 as a proxy for the well-acknowledged risk variant rs1006737) influence psychosocial adaptation in a large German patient sample with schizophrenia-spectrum (n=297) and bipolar (n=516) disorders. We analyzed Global Assessment of Functioning (GAF) scores, retrospectively collected for different time points during disease course. We investigated whether CACNA1C sex-dependently modulates longitudinal GAF scores and recovery from episodes of psychiatric disturbance in the above mentioned disorders. Psychosocial recovery was measured as difference score between the current GAF score (assessing the last remission) and the worst GAF score ever during an illness episode. Covariate- adjusted association analyses revealed a sex x rs10774035 genotype interaction on longitudinal GAF and recovery from illness episodes only in schizophrenia-spectrum but not in bipolar disorders. In schizophrenia-spectrum affected males, rs10774035 minor allele (T) carriers had higher GAF scores at three time points (premorbid, worst ever, current). In contrast, females carrying rs10774035 minor alleles had impaired recovery from schizophrenia-spectrum episodes. These results encourage further investigations of gene x sex interactions and longitudinal quantitative phenotypes to unravel the rich variety of behavioral consequences of genetic individuality.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Human Genetics (Cichon)
UniBasel Contributors:Cichon, Sven
Item Type:Article, refereed
Article Subtype:Research Article
ISSN:1873-7862 (Electronic) 0924-977X (Linking)
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:10 Nov 2018 08:52
Deposited On:10 Nov 2018 08:52

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