title: The Association between COMT, BDNF, and NRG1 and Premorbid Social Functioning in Patients with Psychosis, Their Relatives, and Controls.
abstract: We investigated the influences of putative candidate genes for psychosis on premorbid social adjustment and on premorbid schizoid-schizotypal traits. A family-based sample was used including 177 patients with schizophrenia or bipolar I disorder with a history of psychotic symptoms, 86 of their unaffected relatives, and 116 unrelated healthy controls. Association analyses on the combined sample were conducted using the Statistical Analysis for Genetic Epidemiology software (SAGE) and adjusting for age, sex, clinical group, and the family-based nature of the data. The COMT Val(158)Met and BDNF Val(66)Met polymorphisms showed no evidence of association with either phenotype. The SNP rs221533 of the NRG1 gene was significantly associated with premorbid adjustment in adolescence with TT homozygous subjects having a poorer performance than C allele carriers. In the context of neurodevelopmental disorders such as schizophrenia and other psychoses, this finding is plausible; however, it is preliminary and requires replication in an independent sample. In a broader sense, the use of intermediate quantitative phenotypes such as the ones presented in this study may be of help to understand the mechanism of action of genetic risk factors.
authors.affiliation: NIHR Biomedical Research Centre for Mental Health, South London and Maudsley NHS Foundation Trust and Institute of Psychiatry, Kings College London, P.O. Box 63, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Muriel
authors.initials: M
authors.lastname: Walshe
authors.forename: Evangelos
authors.initials: E
authors.lastname: Vassos
authors.forename: Marco
authors.initials: M
authors.lastname: Picchioni
authors.forename: Madiha
authors.initials: M
authors.lastname: Shaikh
authors.forename: Timothea
authors.initials: T
authors.lastname: Toulopoulou
authors.forename: David
authors.initials: D
authors.lastname: Collier
authors.forename: Colm
authors.initials: C
authors.lastname: McDonald
authors.forename: Robin
authors.initials: R
authors.lastname: Murray
authors.forename: Elvira
authors.initials: E
authors.lastname: Bramon