The Association between COMT, BDNF, and NRG1 and Premorbid Social Functioning in Patients with Psychosis, Their Relatives, and Controls
Muriel Walshe,
Evangelos Vassos,
Marco Picchioni,
Madiha Shaikh,
Timothea Toulopoulou,
David Collier,
Colm McDonald,
Robin Murray,
Elvira Bramon
Affiliations
Muriel Walshe
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
Evangelos Vassos
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
Marco Picchioni
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
Madiha Shaikh
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
Timothea Toulopoulou
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
David Collier
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
Colm McDonald
Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Ireland
Robin Murray
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
Elvira Bramon
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
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 Val158Met and BDNF Val66Met 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.
