In the IMAGEN sample of 2000 adolescent sample from the European cohort, we have detected a strong association between SNP rs16958736 (of VPS4A gene) and the activation of striatum (i.e. caudate, putamen and nucleus accumbens) in 'large win' vs 'no win' contrast of Monetary Incentive Delay (MID) task with P=1.30E-7. A following haplotype analysis then found that the same haplotype that was associated with the activation of striatum was also in association with the hyperactivity (ADHD) assessment from SDQ questionnaire. Meanwhile, in Drosophila, we found that both over-expression and knock-out of VPS4A could alter the frequency of locomotion activity of flies. By searching in the literatures, we then found that VPS4A encodes an ATPase which is involved in trafficking of G protein coupled receptors (GPCRs), including dopamine and noradrenaline. We therefore hypothesize that VPS4A may influence synaptic plasticity through regulating signalling at the dopaminergic and noradrenergic synapse.

In another paper, we have detected the SNP rs2067499 from THRB (Thyroid Hormone Receptor B) in strong association with ACC (anterior cingular cortex) and INS (insula) with P=1.19E-7, the same SNP was then found with significant association with ADHD assessment from SDQ with P=0.014. We propose that a mild resistance to TH (Thyroid Hormone) is associated with increased ACC-INS connectivity and results in ADHD-symptoms by enhancing sensitivity to external and internal stimuli.