Concetta Crisafulli1, Antonio Drago2, Marco Calabrò3, Edoardo Spina4, Alessandro Serretti5. 1. Department of Biomedical Science and Morphological and Functional Images, University of Messina, Messina, Italy. 2. Department of Biomedical and Neuromotor Sciences - DIBINEM, University of Bologna, Bologna, Italy; I.R.C.C.S. "San Giovanni di Dio", Fatebenefratelli, Brescia, Italy. Electronic address: antonio.drago@unibo.it. 3. Department of Biomedical Science and Morphological and Functional Images, University of Messina, Messina, Italy; Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy; IRCCS Centro Neurolesi "Bonino-Pulejo", Messina, Italy. 4. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy. 5. Department of Biomedical and Neuromotor Sciences - DIBINEM, University of Bologna, Bologna, Italy.
Abstract
BACKGROUND: Schizophrenia is a complex mental disorder marked by severely impaired thinking, delusional thoughts, hallucinations and poor emotional responsiveness. The biological mechanisms that lead to schizophrenia may be related to the genetic background of patients. Thus, a genetic perspective may help to unravel the molecular pathways disrupted in schizophrenia. METHODS: In the present work, we used a molecular pathway analysis to identify the molecular pathways associated with schizophrenia. We collected data of genetic loci previously associated with schizophrenia, identified the genes located in those positions and created the metabolic pathways that are related to those genes' products. These pathways were tested for enrichment (a number of SNPs associated with the phenotype significantly higher than expected by chance) in a sample of schizophrenic patients and controls (4486 and 4477, respectively). RESULTS: The molecular pathway that resulted from the identification of all the genes located in the loci previously found to be associated with schizophrenia was found to be enriched, as expected (permutated p(10(6))=9.9999e-06).We found 60 SNPs amongst 30 different genes with a strong association with schizophrenia. The genes are related to the pathways related to neurodevelopment, apoptosis, vesicle traffic, immune response and MAPK cascade. CONCLUSIONS: The pathway related to the toll-like receptor family seemed to play a central role in the modulation/connection of various pathways whose disruption leads to schizophrenia. This pathway is related to the innate immune system, further stressing the role of immunological-related events in increasing the risk to schizophrenia.
BACKGROUND:Schizophrenia is a complex mental disorder marked by severely impaired thinking, delusional thoughts, hallucinations and poor emotional responsiveness. The biological mechanisms that lead to schizophrenia may be related to the genetic background of patients. Thus, a genetic perspective may help to unravel the molecular pathways disrupted in schizophrenia. METHODS: In the present work, we used a molecular pathway analysis to identify the molecular pathways associated with schizophrenia. We collected data of genetic loci previously associated with schizophrenia, identified the genes located in those positions and created the metabolic pathways that are related to those genes' products. These pathways were tested for enrichment (a number of SNPs associated with the phenotype significantly higher than expected by chance) in a sample of schizophrenicpatients and controls (4486 and 4477, respectively). RESULTS: The molecular pathway that resulted from the identification of all the genes located in the loci previously found to be associated with schizophrenia was found to be enriched, as expected (permutated p(10(6))=9.9999e-06).We found 60 SNPs amongst 30 different genes with a strong association with schizophrenia. The genes are related to the pathways related to neurodevelopment, apoptosis, vesicle traffic, immune response and MAPK cascade. CONCLUSIONS: The pathway related to the toll-like receptor family seemed to play a central role in the modulation/connection of various pathways whose disruption leads to schizophrenia. This pathway is related to the innate immune system, further stressing the role of immunological-related events in increasing the risk to schizophrenia.
Authors: Nikkie F M Olde Loohuis; Nael Nadif Kasri; Jeffrey C Glennon; Hans van Bokhoven; Sébastien S Hébert; Barry B Kaplan; Gerard J M Martens; Armaz Aschrafi Journal: Prog Neuropsychopharmacol Biol Psychiatry Date: 2016-02-27 Impact factor: 5.067