A functional NOS1 promoter polymorphism interacts with adverse environment on functional and dysfunctional...

Area of Science:

• Neuroscience
• Behavioral Genetics
• Psychiatry

Background:

• Neuronal nitric oxide synthase (NOS1) knockout mice exhibit increased impulsive aggression.
• A functional promoter polymorphism, NOS1 ex1f-VNTR, is linked to impulsivity-related traits.
• Previous research suggests a connection between NOS1 and impulsivity.

Purpose of the Study:

• To investigate the interaction between the environment and the NOS1 risk allele on impulsivity.
• To determine if adverse conditions modify the effect of the NOS1 ex1f-VNTR genotype on impulsivity measures.

Main Methods:

• A longitudinal population-based cohort study of Estonian pupils (n=435) followed from age 9 to 18.
• Assessment of impulsivity using the Adaptive and Maladaptive Impulsivity Scale, BIS-11, Stop Signal data, and Visual Comparison Test (VCT).
• Collection of data on environmental factors (stressful life events, family environment) and NOS1 ex1f-VNTR genotype.

Main Results:

• The short NOS1 ex1f-VNTR allele was associated with higher adaptive impulsivity, particularly in males.
• Individuals with the risk allele showed poorer performance on the VCT and Stop Signal test.
• Stressful life events and adverse family environment interacted with the risk genotype, increasing maladaptive impulsivity.

Conclusions:

• Short alleles of NOS1 ex1f-VNTR are associated with impulsive behavior.
• Under adverse environmental conditions, the risk genotype increases dysfunctional impulsivity.
• The NOS1 ex1f-VNTR polymorphism may be under balancing selection, explaining its persistence in the population.