No Association Between NRG1 and ErbB4 Genes and Psychopathological Symptoms of Schizophrenia

Sarah Tosato* (Corresponding Author), Martina Zanoni, Chiara Bonetto, Federica Tozzi, Clyde Francks, Elisa Ira, Simona Tomassi, Mariaelena Bertani, Dan Rujescu, Ina Giegling, David St Clair, Michele Tansella, Mirella Ruggeri, Pierandrea Muglia

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)742-751
Number of pages10
JournalNeuroMolecular Medicine
Issue number4
Early online date21 Aug 2014
Publication statusPublished - 1 Dec 2014

Bibliographical note

We are grateful to the patients who participated in the study. We are indebted to the colleagues who contributed to the assessments. This study was supported by the Joint Projects 05 “Towards a new definition of schizophrenia: the biological basis of a core phenotype” with a grant to Mirella Ruggeri from GSK and University of Verona.


  • ErbB4
  • NRG1
  • Psychopathology
  • Schizophrenia


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