The DAT1 gene (also called SLC6A3) encodes the dopamine transporter (DAT) which is a protein responsible for reuptake of dopamine from the synaptic cleft into presynaptic neurons. A variable number tandem repeat (VNTR) polymorphism in the 3′ untranslated region (3′ UTR) of DAT1 has been studied for its role in dopamine regulation, psychiatric disorders, and response to psychotropic medications.

9R/9R Genotype (Homozygous 9R): This genotype is associated with lower DAT expression compared to 10R. This leads to higher synaptic dopamine availability. It is linked to traits such as impulsivity, novelty-seeking, and sometimes greater sensitivity to stimulant medications and may increase vulnerability to substance use disorders. Could cause heightened sensitivity to dopamine-blocking antipsychotics. Individuals may experience extrapyramidal symptoms (EPS), akathisia, agitation, or sedation even at low doses.

10R/10R Genotype (Homozygous 10R): This genotype is associated with higher DAT expression. It results in increased dopamine reuptake and reduced extracellular dopamine levels. Some studies suggest associations with attention-deficit/hyperactivity disorder (ADHD) and altered reward sensitivity. Individuals with this mutation may show different response patterns to stimulant and antipsychotic treatment. Individuals with this genotype may show reduced sensitivity to antipsychotics, potentially requiring higher doses to achieve therapeutic effects. Could experience blunted emotional response or appear treatment resistant.