PMID- 26475575 OWN - NLM STAT- MEDLINE DCOM- 20161005 LR - 20161230 IS - 1873-7862 (Electronic) IS - 0924-977X (Linking) VI - 25 IP - 12 DP - 2015 Dec TI - 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. PG - 2262-70 LID - S0924-977X(15)00307-7 [pii] LID - 10.1016/j.euroneuro.2015.09.012 [doi] AB - 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. CI - Copyright (c) 2015 Elsevier B.V. and ECNP. All rights reserved. FAU - Heilbronner, Urs AU - Heilbronner U AD - Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Germany. Electronic address: urs.heilbronner@med.uni-muenchen.de. FAU - Malzahn, Dorthe AU - Malzahn D AD - Department of Genetic Epidemiology, University Medical Center, Georg-August-University, Gottingen, Germany. FAU - Strohmaier, Jana AU - Strohmaier J AD - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany. FAU - Maier, Sandra AU - Maier S AD - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany. FAU - Frank, Josef AU - Frank J AD - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany. FAU - Treutlein, Jens AU - Treutlein J AD - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany. FAU - Muhleisen, Thomas W AU - Muhleisen TW AD - Institute of Neuroscience and Medicine (INM-1), Research Centre Julich (FZJ), Julich, Germany; Institute of Human Genetics, University of Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. FAU - Forstner, Andreas J AU - Forstner AJ AD - Institute of Human Genetics, University of Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. FAU - Witt, Stephanie H AU - Witt SH AD - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany. FAU - Cichon, Sven AU - Cichon S AD - Institute of Human Genetics, University of Bonn, Germany; Division of Medical Genetics, University Hospital Basel, University of Basel, Switzerland; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. FAU - Falkai, Peter AU - Falkai P AD - Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Germany. FAU - Nothen, Markus M AU - Nothen MM AD - Institute of Human Genetics, University of Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany. FAU - Rietschel, Marcella AU - Rietschel M AD - Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany. FAU - Schulze, Thomas G AU - Schulze TG AD - Institute of Psychiatric Phenomics and Genomics, Ludwig-Maximilians-University Munich, Germany; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany; Department of Psychiatry and Psychotherapy, University Medical Center, Georg-August-University, Gottingen, Germany. LA - eng PT - Journal Article DEP - 20151009 PL - Netherlands TA - Eur Neuropsychopharmacol JT - European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology JID - 9111390 RN - 0 (CACNA1C protein, human) RN - 0 (Calcium Channels, L-Type) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Aged, 80 and over MH - Bipolar Disorder/*genetics MH - Calcium Channels, L-Type/*genetics MH - Female MH - Genetic Predisposition to Disease MH - Humans MH - Longitudinal Studies MH - Male MH - Middle Aged MH - Phenotype MH - Polymorphism, Single Nucleotide/*genetics MH - Psychiatric Status Rating Scales MH - Schizophrenia/*genetics MH - Sex Factors MH - Young Adult OTO - NOTNLM OT - Calcium channel OT - GAF OT - GAS OT - Global assessment of functioning OT - Recovery OT - Schizoaffective EDAT- 2015/10/18 06:00 MHDA- 2016/10/07 06:00 CRDT- 2015/10/18 06:00 PHST- 2015/05/29 00:00 [received] PHST- 2015/08/26 00:00 [revised] PHST- 2015/09/24 00:00 [accepted] PHST- 2015/10/18 06:00 [entrez] PHST- 2015/10/18 06:00 [pubmed] PHST- 2016/10/07 06:00 [medline] AID - S0924-977X(15)00307-7 [pii] AID - 10.1016/j.euroneuro.2015.09.012 [doi] PST - ppublish SO - Eur Neuropsychopharmacol. 2015 Dec;25(12):2262-70. doi: 10.1016/j.euroneuro.2015.09.012. Epub 2015 Oct 9.