The genetics of bipolar disorder have been characterized by non-replication of findings (false positives), inflation of concordance rates in MZ twins, etc. I will post current research on linkage, association and molecular genetic research to help clarify the actual findings and issues involved (neurogenetics is a very complicated field and there is little isomorphism between genotype and phenotype in the field of psychiatry). Below is an abstract of a recent study published in the British Journal of Psychiatry on BDNF (brain-derived neurotrophic factor)- a current focus of research in mood disoders and schizophrenia (it is well documented that chronic stress downregulates the expression of BDNF-and euthymic states potentiate its expression-such as in secure attachment).

Brian Koehler
New York University
QUICK SEARCH:

The British Journal of Psychiatry (2006) 188: 21-25. © 2006
[http://ezproxy.library.nyu.edu:2550/misc/terms.shtml ]The Royal College of Psychiatrists

Genetic variation of brain-derived neurotrophic factor (BDNF) in bipolar disorder

Case-control study of over 3000 individuals from the UK ELAINE K. GREEN, PhD and RACHEL RAYBOULD, BSc

Department of Psychological Medicine, Wales College of Medicine, Cardiff University, Wales, UK

STUART MACGREGOR, PhD

Biostatistics and Bioinformatics Unit, Wales College of Medicine, Cardiff University, Wales, UK

SALLY HYDE, BSc

Division of Neuroscience, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Birmingham, Wales, UK

ALLAN H. YOUNG, MD

Department of Psychiatry, University of Newcastle, Wales, UK

MICHAEL C. O'DONOVAN, PhD, FRCPsych, MICHAEL J. OWEN, PhD, FRCPsych and

GEORGE KIROV, MD, MRCPsych

Department of Psychological Medicine, Wales College of Medicine, Cardiff University, Wales, UK

LISA JONES, PhD

Division of Neuroscience, University of Birmingham, Queen Elizabeth Psychiatric Hospital, Birmingham, Wales, UK

IAN JONES, PhD, MRCPsych and NICK CRADDOCK, PhD, FRCPsych

Department of Psychological Medicine, Wales College of Medicine, Cardiff University, Cardiff, Wales, UK

Correspondence: Professor Nick Craddock, Department of Psychological Medicine, Henry Wellcome Building, Wales College of Medicine, Cardiff University, Heath Park, Cardiff CF4 4XN, UK. Tel: +44 (0)2920 744663; fax: +44 (0) 22920 746554; e-mail: [craddockn@cardiff.ac.uk]

Declaration of interest
N.C. and M.J.O. are consultants to GlaxoSmithKline and have received grant funding and honoraria from GlaxoSmithKline, AstraZeneca and Eli Lilly. M.C. O'D., A.H.Y., L.J. and G.K. have received honoraria from GlaxoSmithKline, AstraZeneca and Eli Lilly. G.K. has received grant funding from Janssen. Funding detailed in Acknowledgements.

Background
Brain-derived neurotrophic factor (BDNF) influences neuronal survival, proliferation and plasticity. Three family-based studies have shown association of the common Valine (Val) allele of the Val66Met polymorphism of the BDNF gene with susceptibility to bipolar disorder.

Aims
To replicate this finding.

Method
We genotyped the Val66Met polymorphism in our UK White bipolar case-control sample (n=3062).

Results
We found no overall evidence of allele or genotype association. However, we found association with disease status in the subset of 131 individuals that had experienced rapid cycling at some time (P=0.004). We found a similar association on re-analysis of our previously reported family-based association sample (P < 0.03, one-tailed test).

Conclusions
Variation at the Val66Met polymorphism of BDNF does not play a major role in influencing susceptibility to bipolar disorder as a whole, but is associated with susceptibility to the rapid-cycling subset of the disorder.