ADHD and Genetics
Twin studies indicate that the disorder is often inherited from the person’s parents, with genetics determining about 75% of cases in children and 35% to potentially 75% of cases in adults. Siblings of children with ADHD are three to four times more likely to develop the disorder than siblings of children without the disorder.
Arousal is related to dopaminergic functioning, and ADHD presents with low dopaminergic functioning. Typically, a number of genes are involved, many of which directly affect dopamine neurotransmission. Those involved with dopamine include DAT, DRD4, DRD5, TAAR1, MAOA, COMT, and DBH. Other genes associated with ADHD include SERT, HTR1B, SNAP25, GRIN2A, ADRA2A, TPH2, and BDNF. A common variant of a gene called latrophilin 3 is estimated to be responsible for about 9% of cases and when this variant is present, people are particularly responsive to stimulant medication. The 7 repeat variant of dopamine receptor D4 (DRD4–7R) causes increased inhibitory effects induced by dopamine and is associated with ADHD. The DRD4 receptor is a G protein-coupled receptor that inhibits adenylyl cyclase. The DRD4–7R mutation results in a wide range of behavioral phenotypes, including ADHD symptoms reflecting split attention. The DRD4 gene is both linked to novelty seeking and ADHD. People with Down syndrome are more likely to have ADHD. The genes GFOD1 and CHD13 show strong genetic associations with ADHD. CHD13’s association with ASD, schizophrenia, bipolar disorder, and depression make it an interesting candidate causative gene. Another candidate causative gene that has been identified is ADGRL3. In zebrafish, knockout of this gene causes a loss of dopaminergic function in the ventral diencephalon and the fish display a hyperactive/impulsive phenotype.
For genetic variation to be used as a tool for diagnosis, more validating studies need to be performed. However, smaller studies have shown that genetic polymorphisms in genes related to catecholaminergic neurotransmission or the SNARE complex of the synapse can reliably predict a person’s response to stimulant medication. Rare genetic variants show more relevant clinical significance as their penetrance (the chance of developing the disorder) tends to be much higher. However their usefulness as tools for diagnosis is limited as no single gene predicts ADHD. ASD shows genetic overlap with ADHD at both common and rare levels of genetic variation.
Evolution may have played a role in the high rates of ADHD, particularly hyperactive and impulsive traits in males. Some have hypothesized that some women may be more attracted to males who are risk takers, increasing the frequency of genes that predispose to hyperactivity and impulsivity in the gene pool. Others have claimed that these traits may be an adaptation that help males face stressful or dangerous environments with, for example, increased impulsivity and exploratory behavior. In certain situations, ADHD traits may have been beneficial to society as a whole even while being harmful to the individual. The high rates and heterogeneity of ADHD may have increased reproductive fitness and benefited society by adding diversity to the gene pool despite being detrimental to the individual. In certain environments, some ADHD traits may have offered personal advantages to individuals, such as quicker response to predators or superior hunting skills. In the Ariaal people of Kenya, the 7R allele of the DRD4 gene results in better health in those who are nomadic but not in those who are settled.
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