BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with a complex aetiology. The identification of candidate intermediate phenotypes that are both heritable and genetically linked to ADHD may facilitate the detection of susceptibility genes and elucidate aetiological pathways. Very low-frequency (VLF; <0.5 Hz) electroencephalographic (EEG) activity represents a promising indicator of risk for ADHD, but it currently remains unclear as to whether it is heritable or genetically linked to the disorder. METHODS: Direct-current (DC)-EEG was recorded during a cognitive activation condition in 30 monozygotic and dizygotic adolescent twin pairs concordant or discordant for high ADHD symptom scores, and 37 monozygotic and dizygotic matched-control twin pairs with low ADHD symptom scores. Structural equation modelling was used to quantify the genetic and environmental contributions to the phenotypic covariance between ADHD and VLF activity. RESULTS: Attention deficit hyperactivity disorder was significantly associated with reduced VLF power during cognitive activation, which suggests reduced synchronization of widespread neuronal activity. Very low-frequency power demonstrated modest heritability (0.31), and the genetic correlation (-0.80) indicated a substantial degree of overlap in genetic influences on ADHD and VLF activity. CONCLUSIONS: Altered VLF activity is a potential candidate intermediate phenotype of ADHD, which warrants further investigation of underlying neurobiological and genetic mechanisms.
BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common and highly heritable neurodevelopmental disorder with a complex aetiology. The identification of candidate intermediate phenotypes that are both heritable and genetically linked to ADHD may facilitate the detection of susceptibility genes and elucidate aetiological pathways. Very low-frequency (VLF; <0.5 Hz) electroencephalographic (EEG) activity represents a promising indicator of risk for ADHD, but it currently remains unclear as to whether it is heritable or genetically linked to the disorder. METHODS: Direct-current (DC)-EEG was recorded during a cognitive activation condition in 30 monozygotic and dizygotic adolescent twin pairs concordant or discordant for high ADHD symptom scores, and 37 monozygotic and dizygotic matched-control twin pairs with low ADHD symptom scores. Structural equation modelling was used to quantify the genetic and environmental contributions to the phenotypic covariance between ADHD and VLF activity. RESULTS: Attention deficit hyperactivity disorder was significantly associated with reduced VLF power during cognitive activation, which suggests reduced synchronization of widespread neuronal activity. Very low-frequency power demonstrated modest heritability (0.31), and the genetic correlation (-0.80) indicated a substantial degree of overlap in genetic influences on ADHD and VLF activity. CONCLUSIONS: Altered VLF activity is a potential candidate intermediate phenotype of ADHD, which warrants further investigation of underlying neurobiological and genetic mechanisms.
Authors: Michael D Fox; Abraham Z Snyder; Justin L Vincent; Maurizio Corbetta; David C Van Essen; Marcus E Raichle Journal: Proc Natl Acad Sci U S A Date: 2005-06-23 Impact factor: 11.205
Authors: Sandra K Loo; Sigi T Hale; Grant Hanada; James Macion; Anshu Shrestha; James J McGough; James T McCracken; Stanley Nelson; Susan L Smalley Journal: J Am Acad Child Adolesc Psychiatry Date: 2010-04 Impact factor: 8.829
Authors: Mizanur Khondoker; Richard Dobson; Caroline Skirrow; Andrew Simmons; Daniel Stahl Journal: Stat Methods Med Res Date: 2013-09-18 Impact factor: 3.021