title: Variations in Disrupted-in-Schizophrenia 1 gene modulate long-term longitudinal differences in cortical thickness in patients with a first-episode of psychosis.
abstract: Schizophrenia patients typically present a widespread bilateral cortical thinning from the early stages of the illness. However, there is controversy whether this reduction in cortical thickness (CT) is static or progressive over the evolution of the disorder. Disrupted-in-Schizophrenia 1 (DISC1) is one of the main candidates genes for schizophrenia, as it has been found associated to the illness, and to several endophenotypes of the disorder including structural brain differences. This gene is known to be involved in neurodevelopment and brain maturation processes. We therefore hypothesized that variations in this gene modulate different progressions of CT in psychosis. Seventy-nine Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs6675281 (Leu607Phe) and rs821616 (Ser704Cys) SNPs of the DISC1 gene. Brain MRIs were carried out at baseline and 3 years after initiating the treatment. Other clinical and socio-demographic variables were recorded to rule out possible confounding effects. Patients homozygous for the Leu allele of the rs6675281 SNP had a significant (p < 0.05) descend in CT over the 3-years period, while those carrying the Phe allele presented an increase in CT. When combining the two SNPs we found a synergic effect on CT progression, presenting those patients homozygous for Leu607 +Ser704 a more pronounced cortical thinning. In conclusion, DISC1 gene variations may modulate the longitudinal changes in cortical thickness in patients suffering from a first episode of non-affective psychosis.
authors.affiliation: Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria, Avda.Valdecilla s/n, 39008, Santander, Spain. javazquez@humv.es.|Centro Investigación Biomédica en Red Salud Mental, CIBERSAM, Madrid, Spain. javazquez@humv.es.|Instituto de Investigación Marqués de Valdecilla, IDIVAL, Santander, Spain. javazquez@humv.es.
authors.forename: Javier
authors.identifier: 0000-0002-5478-3376
authors.initials: J
authors.lastname: Vázquez-Bourgon
authors.affiliation: Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria, Avda.Valdecilla s/n, 39008, Santander, Spain.|Centro Investigación Biomédica en Red Salud Mental, CIBERSAM, Madrid, Spain.|Instituto de Investigación Marqués de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Roberto
authors.initials: R
authors.lastname: Roiz-Santiañez
authors.affiliation: Centro Investigación Biomédica en Red Salud Mental, CIBERSAM, Madrid, Spain.|Departament de Biologia Animal, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain.|Institute of Psychiatric Phenomics and Genomics (IPPG) and Department of Psychiatry-Molecular Neurobiology, Ludwig Maximilian University of Munich, Munich, Germany.
authors.forename: Sergi
authors.initials: S
authors.lastname: Papiol
authors.affiliation: Department of Experimental Clinical Medicine, Inter-University Center for Behavioral Neurosciences (ICBN), University of Udine, Udine, Italy.
authors.forename: Adele
authors.initials: A
authors.lastname: Ferro
authors.affiliation: Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria, Avda.Valdecilla s/n, 39008, Santander, Spain.|Centro Investigación Biomédica en Red Salud Mental, CIBERSAM, Madrid, Spain.|Instituto de Investigación Marqués de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Varela-Gómez
authors.affiliation: Centro Investigación Biomédica en Red Salud Mental, CIBERSAM, Madrid, Spain.|Departament de Biologia Animal, Facultat de Biologia, Institut de Biomedicina de la Universitat de Barcelona (IBUB), Universitat de Barcelona, Barcelona, Spain.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Fañanás
authors.affiliation: Department of Psychiatry, University Hospital Marqués de Valdecilla, School of Medicine, University of Cantabria, Avda.Valdecilla s/n, 39008, Santander, Spain.|Centro Investigación Biomédica en Red Salud Mental, CIBERSAM, Madrid, Spain.|Instituto de Investigación Marqués de Valdecilla, IDIVAL, Santander, Spain.
authors.forename: Benedicto
authors.initials: B
authors.lastname: Crespo-Facorro
mesh_terms: D000208:Acute Disease; D000328:Adult; D002540:Cerebral Cortex / Q000000981:diagnostic imaging*; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009929:Organ Size; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011618:Psychotic Disorders / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000628:therapy; D013030:Spain; D016896:Treatment Outcome; D044465:White People / Q000235:genetics
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins
keywords: Cortical thickness; DISC1; Neuroimaging-genetics; Psychosis; rs6675281; rs821616