Variations in Disrupted-in-Schizophrenia 1 gene modulate long-term longitudinal differences in cortical thickness in patients with a first-episode of psychosis
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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.
KeywordsPsychosis Neuroimaging-genetics Cortical thickness DISC1 rs6675281 rs821616
The present study was performed at the Hospital Marqués de Valdecilla, University of Cantabria, Santander, Spain, under the following Grant support: SENY Fundacio Research Grant 2005, Instituto de Salud Carlos III, FIS 00/3095, 03/1009, PI06/0507, and PI14/00639, and Fundación Marques de Valdecilla A/02/07 and API 07/11. We thank Valdecilla Biobank for providing the biological samples and associated data included in this study and IDIVAL Neuroimaging Unit for its help in the technical execution of this work. We thank the Comissionat per a Universitats i Recerca del DIUE (2014SGR1636), and the Spanish Centro Nacional de Genotipado (CEGEN) for carrying out the genetic analysis.
Conflict of interest
The authors declare that they have no conflict of interest.
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