title: No association between NRG1 and ErbB4 genes and psychopathological symptoms of schizophrenia.
abstract: Neuregulin 1 (NRG1) and v-erb-a erythroblastic leukemia viral oncogene homolog 4 (ErbB4) have been extensively studied in schizophrenia susceptibility because of their pivotal role in key neurodevelopmental processes. One of the reasons for the inconsistencies in results could be the fact that the phenotype investigated has mostly the diagnosis of schizophrenia per se, which is widely heterogeneous, both clinically and biologically. In the present study we tested, in a large cohort of 461 schizophrenia patients recruited in Scotland, whether several SNPs in NRG1 and/or ErbB4 are associated with schizophrenia symptom dimensions as evaluated by the Positive and Negative Syndrome Scale (PANSS). We then followed up nominally significant results in a second cohort of 439 schizophrenia subjects recruited in Germany. Using linear regression, we observed two different groups of polymorphisms in NRG1 gene: one showing a nominal association with higher scores of the PANSS positive dimension and the other one with higher scores of the PANSS negative dimension. Regarding ErbB4, a small cluster located in the 5' end of the gene was detected, showing nominal association mainly with negative, general and total dimensions of the PANSS. These findings suggest that some regions of NRG1 and ErbB4 are functionally involved in biological processes that underlie some of the phenotypic manifestations of schizophrenia. Because of the lack of significant association after correction for multiple testing, our analyses should be considered as exploratory and hypothesis generating for future studies.
authors.affiliation: Section of Psychiatry, Department of Public Health and Community Medicine, University of Verona, Policlinico G.B. Rossi, P.le L.A. Scuro 10, 37134, Verona, Italy, sarah.tosato@univr.it.
authors.forename: Sarah
authors.initials: S
authors.lastname: Tosato
authors.forename: Martina
authors.initials: M
authors.lastname: Zanoni
authors.forename: Chiara
authors.initials: C
authors.lastname: Bonetto
authors.forename: Federica
authors.initials: F
authors.lastname: Tozzi
authors.forename: Clyde
authors.initials: C
authors.lastname: Francks
authors.forename: Elisa
authors.initials: E
authors.lastname: Ira
authors.forename: Simona
authors.initials: S
authors.lastname: Tomassi
authors.forename: Mariaelena
authors.initials: M
authors.lastname: Bertani
authors.forename: Dan
authors.initials: D
authors.lastname: Rujescu
authors.forename: Ina
authors.initials: I
authors.lastname: Giegling
authors.forename: David
authors.initials: D
authors.lastname: St Clair
authors.forename: Michele
authors.initials: M
authors.lastname: Tansella
authors.forename: Mirella
authors.initials: M
authors.lastname: Ruggeri
authors.forename: Pierandrea
authors.initials: P
authors.lastname: Muglia
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use; D015331:Cohort Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005858:Germany; D006801:Humans; D008297:Male; D020890:Neuregulin-1 / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide; D066247:Receptor, ErbB-4 / Q000235:genetics* / Q000502:physiology; D012559:Schizophrenia / Q000188:drug therapy / Q000208:ethnology / Q000235:genetics*; D012606:Scotland; D012720:Severity of Illness Index; D063189:Symptom Assessment; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; C094131:NRG1 protein, human; D020890:Neuregulin-1; C587689:ERBB4 protein, human; D066247:Receptor, ErbB-4