- مبلغ: ۸۶,۰۰۰ تومان
- مبلغ: ۹۱,۰۰۰ تومان
Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder of childhood. It is primarily characterised by high levels of activity, inattention, and impulsivity, and has strong negative impacts on academic functioning. Children with ADHD show a reduction in volume, and hypoactivity, in a range of brain regions. The underlying mechanisms behind these phenotypes are unknown, however, variants in several genes with known roles in neurodevelopment are associated with ADHD. In this review we discuss how these ADHD associated genes contribute to neurodevelopment, and how variants in these genes could give rise to the neurological phenotypes seen in ADHD.
ADHD associated genes participate in all stages of brain development, with those affecting neurotransmission potentially playing a role at every stage. Of course, neurotransmitters have been associated with ADHD for a long time, with the targeting of dopamine reuptake by methylphenidate being the most common medication. The beneficial effects of methylphenidate suggests that neurotransmitter dysregulation contributes to the disorder, but this does not preclude an additional contribution of neurotransmitters during neurodevelopment, and the dysregulation of the dopamine pathway in ADHD may have its origins in the early stages of brain development.
The majority of ADHD associated genes with a known developmental role are involved in the formation and activity of synapses, and disruption of this process is a likely cause of the reduced brain volume observed in ADHD. Furthermore, aberrations in neuronal and axonal migration are consistent with the developmental delay hypothesis. Whilst it is therefore possible to look at cell and animal studies to make a link to the symptoms observed, it is important to note that most of the studies reviewed here involve gene knockout or overexpression systems, while variants detected in ADHD are usually SNPs or variable number tandem repeats. The majority of these variants are found in noncoding regions and, individually, are likely to have very small effects on function. Looking forward, this presents a challenge in modelling ADHD-associated variants, as while it is getting easier to introduce single variants into animal models, we are lacking the necessary assays to detect the small changes in behaviour and physiology that these variants likely cause. Examining multiple variants simultaneously could provide us a way of examining the effects of these variants in a form naturally seen in ADHD, but would not allow dissection of their individual roles. The development of suitable animal models and, importantly, sensitive behavioural assays for these models, will allow further examination of the neurodevelopmental contribution to ADHD, and is a paramount to understanding the disorder as a whole.