1. ¹Developmental Psychiatry, University of Cambridge, Cambridge, UK
2. ²Department of Psychological Medicine, School of Medicine, Cardiff University, Cambridge, UK
3. ³Department of Psychiatry and Genetics, Trinity College Dublin, Dublin, Ireland
4. ⁴MRC Rosalind Franklin Centre for Genomics Research, Cambridge, UK

Correspondence: Dr L Kent, MRCPsych, PhD, Developmental Psychiatry, University of Cambridge, Douglas House, 18b Trumpington Road, Cambridge CB2 2AH, UK. E-mail: lk255@cam.ac.uk

Received 17 December 2004; Revised 2 May 2005; Accepted 3 May 2005; Published online 31 May 2005.

Abstract

Attention deficit hyperactivity disorder (ADHD) is a common, highly heritable, neurodevelopmental disorder with onset in early childhood. Genes involved in neuronal development and growth are, thus, important etiological candidates and brain-derived neurotrophic factor (BDNF), has been hypothesized to play a role in the pathogenesis of ADHD. BDNF is a member of the neurotrophin family and is involved in the survival and differentiation of dopaminergic neurons in the developing brain (of relevance because drugs that block the dopamine transporter can be effective therapeutically). The common Val66Met functional polymorphism in the human BDNF gene (rs 6265) was genotyped in a collaborative family-based sample of 341 white UK or Irish ADHD probands and their parents. We found evidence for preferential transmission of the valine (G) allele of BDNF (odds ratio, OR=1.6, P=0.02) with a strong paternal effect (paternal transmissions: OR=3.2, P=0.0005; maternal transmissions: OR=1.00; P=1.00). Our findings support the hypothesis that BDNF is involved in the pathogenesis of ADHD. The transmission difference between parents raises the possibility that an epigenetic process may be involved.